Dissertations / Theses: 'Carnosinol'

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GILARDONI, ETTORE. "AN INTEGRATED PROTEOMIC AND ANALYTICAL APPROACH FOR ELUCIDATING THE MECHANISM OF ACTION OF HISTIDINE DIPEPTIDES AND SYNTHETIC DERIVATES." Doctoral thesis, Università degli Studi di Milano, 2021. http://hdl.handle.net/2434/797770.

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β-alanil-L-istidina (carnosina) è un peptide endogeno che possiede innumerevoli proprietà (chelante dei metalli, antiossidante, sequestrante delle specie reattive carboniliche). Diversi studi clinici hanno dimostrato un’attività farmacologica della carnosina in malattie su base ossidative, tuttavia il meccanismo dell’attività in vivo non è ancora noto. Questo progetto ha come scopo quello di comprendere il meccanismo in vivo della carnosina. Per far ciò, sono stati sviluppati nuovi metodi analitici di cromatografia liquida accoppiata a spettrometria di massa per la quantificazione in campioni biologici dei peptidi istidinici, loro derivati e gli addotti con le specie reattive carboniliche. Come prima cosa, un metodo analitico basato su una colonna ad interazione idrofiliche è stato sviluppato per l’analisi del carnosinolo in matrici biologiche di modelli animali di sindrome metabolica. La concentrazione di carnosinolo è stata determinata in diversi tessuti e, per la prima volta, l’addotto carnosinolo-acroleina è stato identificato in omogenato di fegato. Questo conferma l’attività del carnosinolo e dei peptidi istidinici come sequestranti delle specie reattive carboniliche in vivo. Tuttavia, è stata identificata l’instabilità metabolica dell’addotto carnosinolo-HNE in diversi tessuti. Saranno quindi necessari ulteriori studi per la caratterizzazione del metabolismo di questi addotti e l’identificazione della corretta entità chimica da ricercare nelle matrici biologiche come indice dell’attività sequestrante di carnosina e derivati. Il metodo basato su colonne ad interazioni idrofiliche è stato anche utilizzato per sviluppare un metodo a rivelazione diretta per determinare l’attività idrolitica del siero umano della carnosina. La carnosinasi serica è stata identificata come principale enzima impiegato nel metabolismo della carnosina. Rispetto ad altri metodi pubblicati in letteratura, quello sviluppato in questo elaborato si basa su una determinazione diretta della carnosina, senza dover effettuare processi complessi di preparazione del campione. I dati ottenuti sono stati convalidati con dati presenti in letteratura, dimostrando che il nostro metodo risulta essere affidabile ed accurato. È stato possibile anche condurre esperimenti di competizione fra substrati naturali e alcune molecole per valutare le principali interazioni substrato/enzima, con l’obiettivo di identificare inibitori della carnosinasi. I dati ottenuti sono stati condivisi con colleghi chimici computazionali che attraverso esperimenti di docking, virtual screening e dinamica molecolare hanno identificato dei possibili inibitori naturali della carnosinasi serica umana. Un nuovo meccanismo d’azione della carnosina è stato approfondito, in quanto recenti pubblicazioni hanno evidenziato un ruolo della carnosina nella prevenzione della formazione di addotti fra la 3,4-diidrofenilglicolaldeide (DOPEGAL), un metabolita intermedio del catabolismo della noradrenalina, e le proteine. La capacità della carnosina di legare covalentemente la DOPEGAL tramite la formazione di un prodotto di Amadori è stata determinata in vitro e in lisato cellulare dove la DOPEGAL è stata formata aggiungendo noradrenalina al lisato enzimaticamente attivo. Studi futuri dovranno caratterizzare la stabilità metabolica di quest’addotto e le caratteristiche della sua formazione in matrici biologiche in quanto risulta essere un interessante biomarcatore di tossicità noradrenalinergica. In fine è stata valutato l’impatto della carnosina e del carnosinolo sul proteoma di cellule endoteliali umane derivanti dalla vena ombelicale. È ormai noto che i farmaci non agiscono unicamente col meccanismo d’azione per il quale sono stati sviluppati, ma possono interferire con l’espressione delle proteine cellulari, aumentandone, o diminuendone l’espressione e di conseguenza attivando o disattivando vie biologiche. Carnosina e carnosinolo non inducono una variazione nell’espressione delle proteine in cellule sane. Questo conferma la sicurezza delle molecole, soprattutto prevedendone un uso come terapia cronica. In futuro l’effetto del trattamento andrà valutato su cellule in condizioni patologiche, per comprendere se, in queste condizioni, carnosina o carnosinolo riescono a influenzare vie metaboliche e risposte cellulari. Sebbene ci siano ancora diverse domande che sono rimaste senza risposta, i dati ottenuti in questo elaborato hanno portato all’aumento della conoscenza del meccanismo d’azione di carnosina e derivati e all’identificazione di composti inibitori della carnosinasi.
β-alanil-L-histidine (i.e. carnosine) is an endogenous peptide that have been extensively characterized for a number of in vitro properties (i.e. metal chelating, antioxidant, reactive carbonyl species quenching). Several clinical trials highlighted the potential benefits of carnosine in the treatment of oxidative stress-based diseases, although the in vivo mechanism of action is not known, yet. The research project herein tries to expand upon the in vivo mechanism of action of carnosine. New analytical methods have been developed by means of liquid chromatography – tandem mass spectrometry for the quantification of histidine dipeptides, their derivatives, and the adducts formed with reactive carbonyl species into biospecimens. A first step was the implementation of hydrophilic interaction chromatography to skip some sample preparation steps and to reduce the chance of systematic errors. The method allowed the quantification of carnosine and carnosinol (a carnosine derivative stable to carnosinase) in biospecimens. Carnosinol tissue distribution in animal models of metabolic syndrome was determined and carnosinol-acrolein adduct was detected for the first time in liver matrices. This finding experimentally confirmed the reactive carbonyl species (RCS quenching activity of histidine dipeptides and derivatives in vivo. However, the metabolic instability of carnosinolHNE adduct was proved and such an evidence requires further studies aiming at understanding the metabolic fate of RCS-adducts to characterize their disposal. Subsequently, a new method for the measurement of carnosine hydrolysis in serum was developed as well. Human serum carnosinase has been identified as the enzyme responsible for such an activity. Compared to other published assays, the method employs a direct detection of the substrate and the use of less sample. Competition experiments with either natural derivatives or other molecules were set to identify hit compounds acting as carnosinase inhibitors. The collected data were shared with computational chemists who identified putative hit compounds via docking, virtual screening, and molecular dynamic approaches. Furthermore, a novel carnosine mechanism of action was studied starting from the evidence that carnosine can prevent the formation of protein adducts with 3,4- dihydroxyphenylglycolaldehyde (DOPEGAL) (i.e. an aldehyde intermediate of norepinephrine metabolism). This could be relevant for the in vivo mode of action of carnosine since DOPEGAL can accumulate in cells because of oxidative stress and as it covalently binds proteins, it can alter their structures and functions. Carnosine quenching activity via the formation of an Amadori product with DOPEGAL was determined in vitro and in cell lysates producing DOPEGAL from enzymatic transformation of norepinephrine. Future studies should be done to characterize the metabolic stability of the adduct and its formation in biospecimens as potential biomarker of norepinephrine toxicity. Finally, the project included proteomics studies on human umbilical vein cells (HUVECs) to assess the impact of carnosine and carnosinol on protein expression. It is widely recognized that drugs exert their pharmacological effects also by an alteration of biological pathways by modifying protein expression. Carnosine and carnosinol have little or no impact on protein expression as detectable on proteome or secretome of healthy endothelial cells. In the future the impact on pathological cells should be carried out as well. These data support the hypothesis of a low toxicity for these molecules, making them suitable candidates for a chronic administration. Although a lot of questions are still unanswered, these data have given new insights in the mechanism of action of carnosine and in the discovery of molecules acting either as carnosine-like compounds or as carnosinase inhibitors.

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Painelli, Vitor de Salles. "Efeitos de 12 semanas de treinamento intermitente de alta intensidade sobre as concentrações intramusculares de carnosina." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/39/39132/tde-30112017-111317/.

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INTRODUÇÃO: A carnosina é um dipeptídeo com capacidade tamponante presente no músculo esquelético, que pode ser obtido pela ingestão de carnes. Estudos transversais relatam que atletas engajados em exercícios de alta intensidade possuem um maior conteúdo de carnosina muscular (CarnM) comparados a destreinados, sugerindo que o treinamento pode modular a CarnM, apesar da ausência de estudos longitudinais. OBJETIVO: Investigar os efeitos do treinamento intermitente (TI) de alta intensidade sobre a CarnM e seus genes associados. MÉTODOS: Vinte homens saudáveis e vegetarianos (eliminando a influência da dieta) foram pareados pelo consumo máximo de oxigênio (VO2máx), e aleatoriamente designados a um grupo Controle (C, N=10) ou Treinado (T, N=10). O grupo T realizou TI em cicloergômetro 3 dias por semana durante 12 semanas, com progressão do volume (6-12 séries) e intensidade (140-170% do limiar de lactato [LL]). O grupo C manteve a rotina habitual. Antes e após a intervenção, biópsias musculares foram realizadas para a determinação da CarnM, da expressão de genes relacionados à CarnM e da capacidade tamponante muscular in vitro (βΜinvitro). Foram realizados teste de Wingate e VO2máx para a avaliação do trabalho total (TT), do VO2máx, dos limiares ventilatórios (LV) e do LL. Foi conduzido o Modelo Misto para análise dos dados. RESULTADOS: Um efeito de interação foi observado para CarnM (F = 4.72; P=0.04), com aumentos significantes para o grupo T (Pré: 15.8±5.7 e Pós: 20.6±5.3 mmoL/kg músculo seco; +36.0%, P=0.01) e nenhuma alteração no grupo C (Pré: 14.3±5.3 e Pós: 15.0±4.9 mmoL/Kg músculo seco; +6.3%, P=0.99). Houve melhora no TT, LV, LL, VO2máx e βΜinvitro no grupo T (todos P<0.05), mas sem mudanças no grupo C (P>0.05). Não houve alteração na expressão gênica das enzimas e transportadores avaliados nos grupos T ou C. CONCLUSÃO: Este estudo sugere que o TI pode aumentar a CarnM, sem alterar os seus genes. Tal aumento, associado ao da βΜinvitro, pode ajudar a explicar o potente efeito deste tipo de treino sobre a aptidão física e cardiorrespiratória
INTRODUCTION: Carnosine is a dipeptide with buffering capacity present within the skeletal muscle, which can be obtained by meat ingestion. Cross-sectional studies report that athletes engaged in high-intensity exercises have a greater muscle carnosine (MCarn) content compared to their untrained counterparts, suggesting that exercise training can modulate MCarn, despite of the absence of longitudinal studies. OBJECTIVE: To investigate the effects of high-intensity intermittent training (HIIT) on CarnM and its associated genes. METHODS: Twenty healthy and vegetarian men (eliminating dietary influences) were matched by maximal oxygen uptake (VO2máx), and randomly assigned to a Control (C, N = 10) or Trained (T, N = 10) group. The T group performed HIIT on cycle ergometer 3 days per week for 12 weeks, with progressive volume (6-12 series) and intensity (140-170% lactate threshold [LT]). The C group kept their usual routine. Prior to the intervention, muscle biopsies were performed for MCarn determination, expression MCarn-related genes and the muscle buffering capacity in vitro (βΜinvitro). Wingate and VO2máx tests were performed to evaluate total work done (TWD), VO2máx, ventilatory thresholds (VT) and LT. The Mixed Model was conducted for data analysis. RESULTS: An interaction effect was observed for MCarn (F = 4.72, P = 0.04), with significant increases for the T group (Pre: 15.8 ± 5.7 and Post: 20.6 ± 5.0 mmoL.kg-1 dry muscle; +36%; P = 0.01), but not in C (Pre: 14.3 ± 5.3 and Post: 15.0 ± 4.9 mmoL.kg-1 dry muscle; +6.3%, P = 0.99). There was no change in the gene expression of the enzymes and transporters evaluated in the T or C groups. There was an improvement in TWD, VT, LT, VO2máx and βΜinvitro in the T group (all P<0.05), but no changes in C (P>0.05). CONCLUSION: This study suggests that HIIT can increase MCarn without altering its genes. This increase, associated with βΜinvitro, may help to explain the potent effect of this type of training on physical and cardiorespiratory fitness

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Oppermann, Henry. "Untersuchungen zur Regulation des Glucosestoffwechsels in Glioblastomen und dessen Beeinflussung durch Carnosin." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-165673.

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Das Glioblastoma multiforme (GBM) ist der am häufigsten vorkommende maligne Hirntumor mit äußerst ungünstiger Prognose für die betroffenen Patienten. Typisch für die Tumore ist eine hohe Aktivität der Glykolyse zur Generierung von ATP und zur Bereitstellung von Makromolekülen für die Zellproliferation, während die oxidative Phosphorylierung auch in Gegenwart von Sauerstoff praktisch keine Bedeutung für die Generation von ATP hat, was auch als Warburg Effekt bekannt ist. Das natürlich vorkommende Carnosin (β-Alanyl-LHistidin) wirkt sich antiproliferativ auf Tumorzellen aus, was mit einer Inhibition der glykolytischen ATP Produktion einhergeht. Der Mechanismus der Inhibition ist weitgehend unverstanden und ist Gegenstand der vorliegenden Arbeit. Im Rahmen der durchgeführten Arbeit wurde der Einfluss von Carnosin auf die mRNA Expressionen von für die Glykolyse relevanten Genen untersucht, wobei eine starke Induktion der Pyruvatdehydrogenase Kinase (PDK) 4 in drei GBM Zelllinien beobachtet wurde. Weiterhin konnte gezeigt werden, dass L-Histidin den gleichen Effekt wie Carnosin zeigt, nicht jedoch β-Alanin, L-Alanin oder L-Alanyl-L-Histidin. Da Tumorzellen die intrazelluläre Gewebscarnosinase aber kaum die extrazelluläre Serumcarnosinase exprimieren, liegt die Vermutung nahe, dass die antineoplastische Wirkung des Carnosins auf die enzymatische Spaltung von Carnosin und die daraus resultierende Freisetzung von L-Histidin zurückzuführen ist. In weiteren Untersuchungen wurden Hinweise erbracht, dass Carnosin durch eine Beeinflussung von Histon-Deacetylasen, die endogene PDK4 mRNA Expression steigern könnte. Zusätzlich wurden die Proteinexpressionen der PDK1 und 4 unter dem Einfluss von Carnosin untersucht.

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Asperger, Ansgar Karl Adam. "Biochemische Untersuchungen zur Wirkung von Carnosin auf das Wachstum humaner Glioblastomzellen." Doctoral thesis, Universitätsbibliothek Leipzig, 2011. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-65568.

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Das Glioblastom ist mit 70 % aller Gliome der häufigste humane Hirntumor mit sehr ungünstiger Prognose. Es konnte gezeigt werden, dass das natürlich vorkommende Dipeptid Carnosin (β-Alanyl-L-histidin) die Proliferation von Glioblastomzellen inhibiert. Diese Wirkung des Carnosins konnte ebenfalls in vivo nachgewiesen werden. Da Carnosin auch einen Einfluss auf den ATP-Haushalt der Glioblastomzellen besitzt, war das Ziel dieser Arbeit einen Wirkungsort von Carnosin zu identifizieren, womit die ATP mindernden und proliferationshemmenden Eigenschaften erklärt werden können. Es wurde untersucht, ob Carnosin den Energiemetabolismus der Glioblastome beeinflusst. Dabei konnte mithilfe zellbiochemischer Methoden gezeigt werden, dass die untersuchten Zelllinien nicht von der Energieversorgung durch die mitochondriale oxidative Phosphorylierung abhängen, da sich weder Hemmung (KCN) noch Entkopplung (DNP) der Elektronentransportkette auf den zellulären ATP-Gehalt auswirkten. Carnosin hingegen verringerte den ATP-Spiegel dieser Zellen. Die Hemmung der Glykolyse durch Oxamat (LDH-Hemmung), bewirkte einen starken Abfall des intrazellulären ATP-Spiegels, worauf Carnosin keinen zusätzlichen Effekt mehr besaß. Carnosin konnte eine Wirkung auf die glykolytische ATP-Synthese zugesprochen werden. Da ein direkter, molekularer Wirkungsort auf diesem Weg nicht identifiziert werden konnte, wurde parallel untersucht, ob sich über Proteomanalysen der Glioblastomzelllinie T98G ein Wirkungsort, bzw. -mechanismus bestimmen lässt. Anhand der Methode der zweidimensionalen Gelelektrophorese (2D-GE) konnten 31 signifikant differenziell exprimierte Proteine detektiert werden, von denen 6 Proteine (VBP-1, OLA-1, TALDO 1, UROD, BAG-2, GRPEL1) über MALDI-TOF-Analysen identifiziert wurden. In Western-Blot-Analysen konnte ein Protein (VBP-1), neben T98G, auch in primären Glioblastomzelllinien als differenziell exprimiert nachgewiesen werden. Anhand der zellbiologischen und proteinbiochemischen Untersuchungen konnte einerseits eine Verbindung des Carnosins zum HIF1α-Signalweg und andererseits zur generellen posttranslationalen Peptidprozessierung hergestellt werden. Der direkte Nachweis eines Einflusses von Carnosin auf HIF1α wurde aber bisher nicht erbracht.

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Painelli, Vitor de Salles. "Influência do estado de treinamento sobre o desempenho físico em resposta à suplementação de beta-alanina." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/39/39132/tde-07072014-155832/.

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Estudos recentes têm demonstrado que a suplementação de beta-alanina (BA) pode melhorar o desempenho físico. O mecanismo proposto para tal resultado envolve o aumento das concentrações intramusculares de carnosina, um dipeptídeo cuja função mais bem atribuída é a de manutenção do equilíbrio ácido-básico. Apesar do emergente corpo literário acerca dos efeitos ergogênicos da suplementação de BA, a maior parte das evidências provém de estudos conduzidos com indivíduos não treinados ou fisicamente ativos, enquanto os estudos com indivíduos treinados são escassos, e seus resultados, controversos. Tem sido especulado que a diferença na capacidade tamponante muscular entre indivíduos treinados e não treinados é um possível fator mascarando o efeito ergogênico da suplementação de BA em indivíduos treinados, já que têm sido demonstrado que este perfil de indivíduos possui maior capacidade tamponante e conteúdo muscular de carnosina. Assim, o objetivo do presente estudo foi investigar a influência do estado de treinamento sobre o desempenho físico intermitente de membros inferiores em resposta à suplementação de BA. Para tanto, 40 homens jovens e saudáveis foram recrutados para participar do estudo, e divididos em dois grupos de acordo com o seu estado de treinamento [ciclistas treinados (T) ou indivíduos não treinados (NT)]. Os participantes foram aleatoriamente designados a um grupo suplementado com BA ou placebo (dextrose - PL), provendo quatro condições experimentais: NTPL, NTBA, TPL e TBA. A suplementação foi realizada com a ingestão de 6.4 gramas de BA ou PL por dia, durante 4 semanas. Antes e após o período de suplementação, os participantes completaram 4 séries do teste de Wingate para membro inferior, com 30 segundos de duração cada uma e 3 minutos de descanso entre elas. O trabalho total realizado foi significantemente aumentado após o período de suplementação em ambos os grupos NTBA (+1349 ± 1411 kJ; P = 0.03) e TBA (+1978 ± 1508 kJ; P = 0.002), foi significantemente reduzido no grupo NTPL (-1385 ± 2815 kJ; P = 0.03), e não se alterou no grupo TPL (-219 ± 1507 kJ; P = 0.73). Comparada ao período pré-suplementação, a potência média no período pós-suplementação foi significantemente maior na série 4 para o grupo NTBA (P = 0.0004), enquanto a mesma foi maior nas séries 1, 2 e 4 (P <= 0.05) para o grupo TBA. Não foram observadas diferenças na potência média entre o período pré- e pós-suplementação para os grupos NTPL e TPL. Em conclusão, quatro semanas de suplementação de BA foram efetivas em melhorar o desempenho físico intermitente de membros inferiores em ambos os participantes treinados e não treinados. Estes dados ressaltam a eficácia ergogênica da suplementação de BA para exercícios de alta-intensidade, independentemente do estado de treinamento do indivíduo
Recent studies have demonstrated that beta-alanine (BA) supplementation can improve performance. The proposed mechanisms for this result involve an increased muscle carnosine content, a dipeptide whose function is attributed to the maintenance of acid-base balance. Even though the body of evidence surrounding the ergogenic effects of BA supplementation is increasing, most of the evidences come from studies conducted with physically active or untrained individuals, while studies with trained participants are scarce, and their results, controversial. It has been speculated that the difference in muscle buffering capacity between trained and untrained individuals is a possible factor masking the ergogenic effect of BA supplementation in trained individuals, who have already been demonstrated to have greater buffering capacity and muscle carnosine content. Therefore, the aim of this study was to investigate the influence of training status on intermittent lower-body performance in response to BA supplementation. For this purpose, forty young males were divided into two groups according to their training status (trained - T, and untrained - NT cyclists). Participants were further randomly allocated to BA or placebo (dextrose - PL) groups, providing four experimental conditions: NTPL, NTBA, TPL, TBA. BA or PL was ingested by 6.4 g·d-1, during for 4 weeks. Before and after the supplementation period, participants completed four 30-seconds lower-body Wingate bouts, separated by 3 minutes. Total work done was significantly increased following supplementation in both NTBA (+1349 ± 1411 kJ; P = 0.03) and TBA (+1978 ± 1508 kJ; P = 0.002), and it was significantly reduced in NTPL (-1385 ± 2815 kJ; P = 0.03) with no difference for TPL (-219 ± 1507 kJ; P = 0.73). Compared to pre-supplementation, post-supplementation mean power output was significantly higher in bout 4 for NTBA (P = 0.0004), and higher in bouts 1, 2 and 4 (P <= 0.05) for TBA. No differences were observed in mean power output for NTPL and TPL from pre- to post-supplementation period. In conclusion, four weeks of BA supplementation was effective at improving intermittent lower-body performance in both untrained and trained individuals. These data highlight the efficacy of BA as an ergogenic aid for high-intensity exercise regardless of the training status of the individual

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Rocha, Carolina Camargo. "Identificação e quantificação da carnosina no plasma seminal, características seminais e congelabilidade do sêmen de garanhões." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-17052017-145008/.

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A criação de equinos tem se desenvolvido ativamente no Brasil. Assim, o interesse dos proprietários em biotecnologias reprodutivas equinos vem aumentando. Entretanto, o sêmen equino tem baixa tolerância à criopreservação comparada com outras espécies, sendo o estresse oxidativo um entrave por seus efeitos deletérios sobre a célula espermática. Neste contexto, o plasma seminal possui antioxidantes que promovem um papel importante na proteção do espermatozoide. Porém o, durante o processo de criopreservação, o plasma seminal é retirado. Em estudo anterior verificamos que, na ausência do plasma seminal os espermatozoides equinos tornam-se mais susceptíveis ao estresse oxidativo, principalmente causado pelo malondialdeído (MDA), subproduto da oxidação de lipídeos. Um dos motivos para este resultado seria a retirada da carnosina, um dos principais antioxidantes responsáveis pela proteção contra o acúmulo de MDA e seus efeitos deletérios, presente no plasma seminal. O objetivo do presente estudo é identificar e quantificar carnosina no plasma seminal de garanhões e comparar as características seminais em diferentes grupos de bons e maus refrigeradores e congeladores, baseando-se na análise da motilidade posterior ao processo de refrigeração e congelação. Foram colhidos dois ejaculados de quarenta garanhões (idades entre 4 e 16 anos de idade). As variáveis analisadas foram cinética espermática pelo sistema CASA, avaliação funcional (coloração de eosina-nigrosina para membranas, fast-green/rosa bengala para acrossomos, coloração 3-3diaminobenzidina para atividade mitocondrial e SCSA™ para susceptibilidade a denaturação de cromatina) e avaliação do índice de peroxidação lipídica (TBARS) do espermatozoide e do plasma seminal. Também foram realizadas análises da integridade de membranas plasmática e acrossomal, e potencial de atividade mitocondrial pelas sondas fluorescentes PI, Hoescht 33342, FITC-PSA e JC-1 além da produção de (ROS) pelo espermatozoide com a sonda fluorescente CellRox. A carnosina do plasma seminal foi mensurada utilizando kit de ELISA Biomatik® comercial. Foram comparados os grupos bons e maus refrigeradores, e bons e maus congeladores (p≤0,05). Verificamos uma maior concentração de carnosina nos bons refrigeradores em relação aos que refrigeraram mau. Isso pode ter ocorrido pela maior concentração de TBARS no plasma seminal destes animais, possivelmente por um efeito fisiológico de reações de oxidação. Além disto, os bons refrigeradores apresentaram porcentagens significativamente maiores de células com alta atividade mitocondrial, acrossomo intacto e membrana intacta sugerindo um efeito benéfico da carnosina. Em relação ao efeito da congelação do sêmen, não foi observada diferença na concentração de carnosina entre os que congelaram bem ou não. Este resultado era esperado uma vez que, durante o processo de criopreservação do sêmen equino o plasma seminal é retirado. De fato, a maior porcentagem de células com lesão mitocondrial, de membrana e DNA lesado nos maus congeladores e as correlações entre as lesões e o estresse oxidativo pode indicar um mecanismo mitocondrial de geração de estresse oxidativo e consequente lesão das estruturas celulares. Conclui-se que a carnosina apresentou efeito protetor durante a refrigeração espermática protegendo contra injúrias causadas pela mesma e consequentemente é um dos fatores que melhora a qualidade espermática após 24 horas de refrigeração.
Equine breeding has been actively developing in Brazil, leading to increased interest in reproductive biotechnology. However, there is a limitation due to a tolerance of some stallions to cryopreservation, especially when compared to other species. In this context, oxidative stress represents an obstacle due to its deleterious effects on equine sperm. To counterattack such effect, seminal plasma has antioxidants that play an important role in protecting the sperm. However, during the cryopreservation process, the seminal plasma is withdrawn. In a previous study we verified that, in the absence of seminal plasma, equine spermatozoa are more susceptible to oxidative stress, mainly caused by malondialdehyde (MDA), a product of lipid oxidation. One of the reasons for this result would be the removal of carnosine present in the seminal plasma, one of the main antioxidants responsible for protection against the MDA accumulation and its deleterious effects. The objective of the present study was to identify and quantify carnosine in the seminal plasma of stallions and to compare the seminal characteristics in different groups of sperm samples with high and low tolerance to the cryopreservation or cooling, based on analysis of total motility after these processes. Two ejaculates of forty stallions (N= 80; ages between 4 and 16 years old) were collected. Each ejaculate was divided into two aliquots, one submitted to a 24h cooling and the other submitted to cryopreservation. The variables analyzed were: Computer Assisted Sperm Analysis (CASA system), functional evaluation (eosin-nigrosin stain for membranes, fast-green/rose bengal for acrosomes, 3-3\'diaminobenzidine staining for mitochondrial activity and SCSA™ for susceptibility to chromatin denaturation) and lipid peroxidation index (TBARS assay) of sperm and seminal plasma. Furthermore, plasma and acrossomal membranes integrities and mitochondrial membrane potential were also analyzed using the fluorescence probes PI, Hoescht 33342, FITC-PSA, JC-1 and ROS detection by CellRox fluorescent probes. Carnosine from the seminal plasma was measured using commercial Biomatik® ELISA kit. Thus, samples with high and low tolerance were compared (p≤0.05). We found a higher concentration of carnosine in good cooler compared to those showing low motility. This may have occurred in response to the higher concentration of TBARS in the seminal plasma of these animals, possibly due to a physiological effect of oxidation reactions. In addition, good coolers presented significantly higher percentages of cells with high mitochondrial activity, intact acrosome and intact membrane suggesting a beneficial effect of carnosine. Regarding the effect cryopreservation, no difference was observed between those with high and low post-thaw motility. This result was expected since, during the cryopreservation process of equine semen, the seminal plasma is removed. In fact, the higher percentage of cells with mitochondrial lesions, damaged membrane and fragmented DNA in bad freezers and the correlations between lesions and oxidative stress may indicate a mitochondrial mechanism of oxidative stress generation and consequent lesion of cellular structures. In conclusion, carnosine had a protective effect during sperm cooling, protecting against damages being probably one of the factors that improves sperm quality after 24 hours of refrigeration.

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7

Mangoni, Ana Paula. "Materiais híbridos baseados em argilas catiônicas e espécies com potencial terapêutico." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/46/46136/tde-30042014-141506/.

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Os argilominerais são empregados na área farmacêutica e cosmética tanto como excipientes quanto ingredientes ativos. Esses compostos inorgânicos são inertes quimicamente, apresentam estruturas definidas e alta estabilidade térmica, o que contribui para o uso nessas áreas. Atualmente a indústria farmacêutica busca modificações no sistema de entrega de drogas (melhorias no tempo, local e taxa de liberação), objetivando um aumento na estabilidade das drogas e a prevenção e diminuição de efeitos colaterais. Nesse sentido, surge a necessidade de desenvolver novas formulações farmacêuticas, novos métodos de preparação e novos materiais. Considerando o fato dos argilominerais incorporarem espécies diversas entre suas lamelas, é interessante explorar a possibilidade de uso dessas matrizes inorgânicas como carregadores de espécies bioativas. O principal objetivo do presente trabalho foi preparar e caracterizar argilas de uso farmacêutico e/ou cosmético intercaladas com espécies que apresentam potencial terapêutico. Para tanto, usou-se duas argilas esmectitas naturais do tipo montmorilonita (Cloisita Sódica e Veegum HS) e uma esmectita sintética do tipo hectorita (Laponita RD). Os aminoácidos L-lisina, L-arginina e L-ornitina, e o dipeptídeo L-carnosina foram imobilizados em argilas catiônicas, por meio de reação de troca iônica. Na preparação dos materiais híbridos, alguns parâmetros experimentais foram avaliados: concentração hidrogeniônica (pH) da suspensão de reação, proporção argila/aminoácido e tempo de reação. As argilas precursoras e os materiais híbridos obtidos foram caracterizados por difratometria de raios X, espectroscopia vibracional na região do infravermelho e Raman, análise termogravimétrica acoplada à espectrometria de massas e análise química de carbono. Os valores de distância interlamelar (d(001)) dos materiais sugerem que a cadeia carbônica das espécies orgânicas se orienta paralelamente em relação às lamelas de baixa densidade de carga dos argilominerais. Nos espectros vibracionais na região do infravermelho há predominância das bandas características da estrutura inorgânica, mas as bandas entre 1800 e 1400 cm-1 relativas aos grupos funcionais do aminoácido permitem inferir sobre o seu grau de protonação no material híbrido. A acidez de Brönsted gerada pela polarização das moléculas de água associadas à argila foi observada para as montmorilonitas empregadas neste estudo. Amostras preparadas em suspensões nas quais o valor do pH era maior que o valor da primeira constante ácida (pKa1) dos aminoácidos apresentam bandas atribuídas ao estiramento C=O de grupo carboxilato protonado. Os espectros Raman foram obtidos apenas para a argila sintética, uma vez que as naturais apresentam luminescência. O espectro Raman da L-carnosina imobilizada em Laponita indica a presença preponderante da espécie zwitteriônica; o deslocamento das bandas atribuídas aos grupos amida e carboxílico do dipeptídeo para região de menor energia sugere a formação de ligações de hidrogênio com os grupos silanol da Laponita. Os resultados de análise termogravimétrica acoplada à espectrometria de massas dos materiais híbridos são distintos daqueles observados para os aminoácidos livres. A temperatura de início de decomposição das espécies orgânicas não é praticamente modificada após imobilização nas argilas, mas os processos térmicos se estendem até regiões de maior temperatura, evidenciando a influência da estrutura inorgânica sobre a decomposição térmica dos aminoácidos. Através dos dados de quantidade de carbono e de água nas amostras, calculou-se a concentração de aminoácidos nos materiais híbridos (massa de aminoácido / 100 gramas de material). As maiores concentrações de aminoácido (entre seis e oito por cento) foram observadas para as amostras de Cloisita e Veegum HS, isoladas em condições nas quais predomina a interação eletrostática entre as lamelas e os aminoácidos com carga positiva. Nas condições experimentais empregadas neste trabalho não foi observada a saturação das argilas com os aminoácidos, ou seja, as cargas das lamelas não foram totalmente neutralizadas pelos íons orgânicos.
Clay minerals are used as excipients or active ingredients in the pharmaceutical and cosmetic fields. These inorganic compounds are chemically inert, have defined structures and high thermal stability, which make them useful for these areas. Currently the pharmaceutical industry seeks modifications in the drug delivery systems (improvements in the time, place and rate of release), aiming an increase in the stability of the drugs and also the prevention and reduction of side effects. In this way, it is a need to develop new pharmaceutical formulations, new preparation methods and new materials. Considering the fact that clay minerals incorporate various species between their layers, it is interesting to explore the possibility of using these inorganic matrices as carriers of bioactive species. The main aim of this work was to prepare and characterize clays of pharmaceutical and/or cosmetic usage intercalated with species of therapeutic potential. Two natural smectite clays of montmorillonite type (Sodium Cloisite and Veegum HS) and one synthetic smectite of hectorite type (Laponita RD) were employed. The amino acids L-lysine, L-arginine and L-ornithine, and the L-carnosine dipeptide were immobilized on cationic clays by ion exchange reaction. Some experimental parameters were evaluated in the preparation of hybrid materials: hydrogen ion concentration (pH) of reaction suspension, clay/amino acid proportion and reaction time. Pristine clays and hybrid materials were characterized by X-ray diffraction, infrared and Raman vibrational spectroscopies, thermogravimetric analyses coupled to mass spectrometry and chemical analysis of carbon. The materials values of interlayer distance (d(001)) suggest that the carbon chain of the organic species is oriented parallel to the layers of clay minerals. The infrared vibrational spectra are dominated by the inorganic structure bands; however the bands between 1800 and 1400 cm-1 related to the functional groups of the amino acid allow to infer about the protonation degree in the hybrid material. The Brönsted acidity generated by the polarization of water molecules associated with the clay was observed for montmorillonite samples used in this study. Materials prepared in suspensions in which the pH value was greater than the value of the first acid constant (pKa1) show bands assigned to the C=O stretching of protonated carboxylate group. Raman spectra were obtained only for the synthetic clay, since the natural ones luminesce. Raman spectrum of L-carnosine immobilized on Laponita indicates the presence of mostly zwitterionic species; the displacement of bands assigned to amide and carboxylic groups of the dipeptide to the lower energy region suggests the formation of hydrogen bonds with the Laponita silanol groups. The results of thermogravimetric analyses coupled to mass spectrometry of hybrid materials are different from those observed for the free amino acids. The onset temperature of the organic species decomposition is practically unmodified after the immobilization on clays, but thermal processes are postponed up to higher temperature, revealing the inorganic structure influence on the amino acids thermal decomposition. Data on the carbon and water amounts in the samples were used to calculate the concentration of amino acids in the hybrid materials (mass of amino acid / 100 grams of material). The highest concentrations of amino acid (between six and eight percent) was observed for Cloisite and Veegum HS samples, isolated under conditions in which the electrostatic interaction between the layers and the positively charged amino acids are predominant. Under the experimental conditions employed in this study no saturation of clay with amino acids was observed, i.e. the layer charges were not completely neutralized by the organic ions.

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8

Milioni, Fabio. "Influência da suplementação de β-alanina associada ao treinamento intervalado de alta intensidade no desempenho de sprints repetidos." Universidade Estadual Paulista (UNESP), 2018. http://hdl.handle.net/11449/157220.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O objetivo da presente tese foi verificar a influência da suplementação de β-Alanina associado ao treinamento intervalado de alta intensidade (HIIT) na performance de sprints repetidos. Participaram do estudo conduzido em caráter randomizado e duplo-cego, 20 jovens saudáveis alocados em dois grupos (Gβ [n = 10] – 6,4 g.dia-1 de β-Alanina; GP [n = 10] – 6,4 g.dia-1 de dextrose - placebo). Os participantes foram avaliados em três momentos distintos, previamente ao início, após quatro semanas de HIIT sem suplementação e após 6 semanas de suplementação + HIIT. As avaliações foram compostas por teste incremental até exaustão (TINC); séries de 12 sprints repetidos (RSA); e teste de tempo limite até exaustão a 115% da velocidade máxima atingida no TINC (TLIM). Previamente e imediatamente após TINC e RSA foram realizadas avaliações neuromusculares compostas por saltos verticais máximos, contrações isométricas máximas de extensão de joelho e estimulação elétrica periférica. O HIIT foi composto de dez corridas de 1 min a 90% da velocidade máxima atingida no TINC, com 1 min de recuperação passiva entre as corridas e frequência de 3 sessões semanais. Previamente ao início da suplementação + HIIT e ao final da intervenção, os participantes foram submetidos a biópsias musculares para determinação do conteúdo de carnosina intramuscular, capacidade de tamponamento in vitro e conteúdo de proteínas/enzimas chaves. Após a intervenção, ambos os grupos melhoraram o metabolismo oxidativo (i.e., consumo máximo de oxigênio), entretanto, somente o Gβ melhorou significativamente o conteúdo de carnosina intramuscular e as variáveis do RSA além de apresentar atenuação da fadiga neuromuscular induzida pelo RSA. Não foram verificadas diferenças significativas na capacidade anaeróbia, capacidade de tamponamento in vitro e conteúdo de proteínas/enzimas chaves. Dessa forma, a associação entre suplementação de β-Alanina e HIIT proporcionou melhora significativa do desempenho de sprints repetidos.
The aim of the present thesis was to verify the influence of β-Alanine supplementation associated with high intensity interval training (HIIT) on the performance of repeated sprints. The study was conducted in a randomized, double-blind design and 20 healthy young men were allocated in two groups (Gβ [n = 10] - 6.4 g.day-1 of β-Alanine; GP [n = 10] - 6.4 g.day-1 of dextrose – placebo). The participants were evaluated at three different moments, prior to beginning, after four weeks of HIIT without supplementation and after 6 weeks of supplementation + HIIT. The evaluations were composed by incremental test until exhaustion (TINC); set of 12 repeated sprints (RSA); and time-to-exhaustion test at 115% of the maximum velocity achieved in TINC (TLIM). Previously and immediately after TINC and RSA, neuromuscular evaluations were performed, consisting of maximum vertical jumps, maximal voluntary isometric contractions of knee extension and peripheral electrical stimulation. The HIIT was composed by ten runs of 1-min at 90% of the maximum velocity achieved in TINC, with 1-min of passive recovery between runs and frequency of 3 sessions per week. Prior to the initiation of supplementation + HIIT and at the end of the intervention, the participants underwent muscle biopsies to determine intramuscular carnosine content, muscle buffer capacity in vitro and key protein/enzyme content. After the intervention, both groups improved oxidative metabolism (i.e., maximal oxygen uptake), however, only Gβ significantly improved the intramuscular carnosine content and the RSA variables; in addition to presenting attenuation of the neuromuscular fatigue induced by the RSA. No significant differences were observed in anaerobic capacity, muscle buffer capacity in vitro and key protein/enzyme content. Thus, the association between β-Alanine supplementation and HIIT provided significant improvement in repeated sprints performance.
2016/02683-6

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9

Brisola, Gabriel Motta Pinheiro [UNESP]. "Efeitos da suplementação de β-alanina sobre a potência anaeróbia, habilidade de esforços repetidos e desempenho no polo aquático." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/144686.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O objetivo geral do presente trabalho foi verificar o potencial ergogênico da suplementação por 4 semanas de β-alanina sobre a potência anaeróbia, habilidade de esforços repetidos e desempenho no polo aquático. 22 jogadores de elite do sexo masculino (média±dp: idade = 18±4 anos, peso = 78,5±9,5 kg e altura = 1,79±0,06 m) participaram do estudo, que foi conduzido de modo randomizado, duplo cego e placebo controlado. Os participantes foram divididos em dois grupos (β-alanina e placebo) de 11 atletas cada e foram submetidos a testes específicos (teste de habilidade de esforços repetidos (RSA) e teste máximo de 30s de salto sob o gol (30CJ)) e semi-específicos (teste de 30s máximo em nado atado (30ATADO), teste máximo de 3 minutos (All Out 3min), teste incremental máximo (GXTATADO) e performance de 200m em nado crawl (P200m)) para a modalidade e um jogo simulado para possibilitar o rastreamento das atividades realizadas por meio de filmagem. As avaliações ocorreram pré e após o período de suplementação (4 semanas). Não foram encontrados efeitos significativos de interação entre os grupos para nenhuma variável do presente estudo. No entanto, alguns ligeiros indícios de melhora com a suplementação de β-alanina foram encontrados como: (1) melhora significativa entre os momentos (pré × pós) no número total de sprints durante o jogo simulado de polo aquático; (2) efeito provavelmente benéfico (análise de inferência baseada na magnitude) para o tempo médio, pior tempo e tempo total na primeira série do teste de RSA (RSA1); (3) melhora significativa entre os momentos na força média e integral de força durante o teste 30ATADO e na P200m; (4) melhora significativa entre os momentos na força pico no teste GXTATADO. Portanto, conclui-se que a suplementação por 4 semanas de β-alanina pode promover apenas melhorar ligeiramente alguns parâmetros relacionados a habilidade de nado no polo aquático como número total de sprints em jogo simulado, tempo médio, pior tempo e tempo total no teste de RSA, força média e integral de força no 30ATADO, P200m e força crítica no GXTATADO.
The overall aim of this study was to investigate the ergogenic effect of 4 weeks β-alanine supplementation on the anaerobic power, ability to performed repeated efforts and performance of water polo. 22 male elite players (mean±SD age = 18±4 years, weight = 78.5±9.5 kg and height = 1.79±0.06 m) participated in the study, which was conducted in order randomized, double blind and placebo controlled. Participants were divided into two groups (β-alanine and placebo) of 11 athletes each and were subjected to specific tests (repeated sprint ability test (RSA) and maximum 30s jump under the goal test (30CJ)) and semi-specific (30s maximal test in tethered swimming (30TS), maximal 3 min effort (AllOut-3min), tethered swimming graded exercise test (GXTTS) and 200m in front crawl (P200m)) for the modality and a simulated game to enable tracking of the activities carried out by video record. Assessments occurred before and after the supplementation period (4 weeks). There were no significant interaction effects between the groups for any variable of this study. However, some slight improvement indications with β-alanine supplementation were found to: (1) significant improvement between moments (pre × post) the total number of sprints during the simulated game water polo; (2) probably beneficial effect (magnitude-based inference analysis) for the mean time, worst time and total time in the first series of the RSA test (RSA1); (3) significant improvement between moments for mean force and integral of force during the 30TS and P200m; (4) significant improvement between moments for peak power at GXTTS. Therefore, it is concluded that supplementation for 4 weeks of β-alanine can promote only slightly improve some parameters related to swimming ability in water polo as total number of sprints in simulated game, mean time, worst time and total time on test RSA, mean and integral of force in 30TS, P200m and critical force in GXTTS.
FAPESP: 2014/02186-7

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10

Kawai, Giulia Kiyomi Vechiato. "Efeito da carnosina na prevenção de crioinjúrias no sêmen de garanhões bons e maus congeladores." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/10/10131/tde-04052017-104658/.

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As espécies reativas de oxigênio são fundamentais na fisiologia espermática. No entanto, um desequilíbrio entre a produção e a capacidade antioxidante caracteriza o estresse oxidativo (EO). O espermatozoide é extremamente suscetível ao EO pois, dentre outras características, a membrana plasmática é rica em ácidos graxos poli-insaturados responsáveis por promoverem a fluidez necessária em processos fisiológicos como motilidade e fertilização. Por outro lado, essas insaturações são mais facilmente oxidadas e vulneráveis à peroxidação lipídica. Em função desta susceptibilidade, estas células dependem fortemente de compostos presentes no plasma seminal (PS) para a proteção contra esse evento. Dessa forma, a carnosina, dipeptídeo presente no PS pode ser uma das responsáveis pela proteção contra o acúmulo do MDA. No entanto, durante a criopreservação do sêmen equino é necessário retirar o PS. Em estudo recente, verificamos que esta remoção, torna os espermatozoides sensíveis ao subproduto extremamente deletério da peroxidação lipídica, o malondialdeído (MDA). Como a carnosina é removida junto com o plasma seminal durante a criopreservação, foram desenvolvidos 2 experimentos sequenciais visando a melhora da qualidade do sêmen criopreservado com adição de carnosina. Amostras de sêmen de sete garanhões foram tratadas com concentrações crescentes de carnosina adicionadas ao diluidor (1mM, 50mM e 100mM). Após a descongelação, as amostras foram divididas retrospectivamente em grupos de alta congelabilidade (AC: motilidade maior que 30%) e baixa congelabilidade (BC: motilidade menor que 30%). Amostras tratadas com 50mM apresentaram menor porcentagem de células com lesão de membrana plasmática e, quando tratadas com 100mM, células com maior amplitude do deslocamento lateral de cabeça. Amostras controle BC apresentaram menor porcentagem de células com DNA íntegro em relação às amostras AC. No entanto, houve um leve aumento na porcentagem de células com DNA íntegro em amostras BC com 100mM, não diferindo das amostras AC. Por outro lado, amostras BC criopreservadas com 50mM apresentaram maiores porcentagens de células com escore calculado de potencial de membrana mitocondrial e mais suscetíveis ao EO em relação ao controle. Apesar da proteção parcial, a maior suscetibilidade à peroxidação lipídica torna-se um problema, especialmente pelo fato de que espermatozoides equinos são mais suscetíveis ao MDA. Um motivo para este efeito seria a afinidade da carnosina em reagir com açúcares, o que poderia influenciar negativamente a atividade mitocondrial e o status oxidativo, ao diminuir a produção de piruvato pela via glicolítica. Desta forma, no experimento 2, amostras BC foram tratadas com a combinação de carnosina (0 e 50mM) e piruvato (0 e 5mM) em arranjo fatorial 2x2. Verificou-se que o tratamento com piruvato (5mM) proporcionou menos células com baixa atividade mitocondrial. Por outro lado, a carnosina (50mM), promoveu maior motilidade total, progressiva e células rápidas. Houve uma tendência de aumento nas células com velocidade progressiva e atividade mitocondrial na combinação de tratamentos. Não houve diferença entre os grupos na suscetibilidade ao EO que, no entanto, correlacionou-se negativamente com células móveis, rápidas e integridade de membrana plasmática e acrossomal. Estes resultados indicam que subprodutos da peroxidação lipídica, sendo o principal deles o MDA, podem causar danos ao DNA, às mitocôndrias e à cinética espermática. Neste contexto, a carnosina (100mM) parece ter um leve efeito protetor ao DNA contra o acúmulo de MDA. Além disto, 50mM de carnosina parece auxiliar na manutenção da velocidade progressiva e atividade mitocondrial quando associada ao piruvato (5mM). Assim, a carnosina e o piruvato podem ser utilizados na prevenção de crioinjúrias em amostras de baixa congelabilidade.
Reactive oxygen species (ROS) plays a key role in the sperm physiology. However, an imbalance between ROS production and antioxidant capacity characterize the oxidative stress (OE). The spermatozoa are extremely susceptible to EO because, among other characteristics, the plasma membrane is rich in polyunsaturated fatty acids responsible for promoting fluidity necessary in physiological processes such as motility and fertilization. However, these unsaturations are more easily oxidized and vulnerable to lipid peroxidation. Due to this susceptibility, these cells strongly depend on compounds present in the seminal plasma (SP) to protect against this event. Thus, carnosine, a dipeptide present in SP of stallions, may be a key factor on the protection against MDA accumulation. Nevertheless, during the equine sperm cryopreservation process, SP is removed. In a recent study, we observed that seminal plasma removal led to an increased susceptibility of equine spermatozoa to extremely deleterious product of lipid peroxidation, malondialdehyde (MDA). As the carnosine is removed together with the seminal plasma during cryopreservation, two sequential experiments were developed aiming to improve the quality of stallion cryopreserved semen by means of carnosine therapy. Samples from seven stallions were treated with increasing concentrations of carnosine added to the extender (1mM, 50mM and 100mM) and submitted to cryopreservation. After thawing, samples were classified as high freezeability (HF: total motility greater than 30%) and low freezeability (LF: total motility lower than 30%). Samples treated with 50mM presented lower percentage of sperm showing plasma membrane damage and, when treated with 100mM, a greater amplitude of the lateral head displacement was observed. Untreated LF samples showed a lower percentage of cells showing intact DNA in relation to HF samples. By contrast, when LF samples were treated with 100mM, there was an increase in the percentage of cells with intact DNA, which was similar to the HF samples. On the other hand, LF samples cryopreserved with 50mM had a higher percentage of cells showing high calculated mitochondrial membrane potential score and increased susceptibility to OE in relation to the control. Despite the partial protection, the increased susceptibility to lipid peroxidation is a concern since equine spermatozoa is highly vulnerable to the MDA. Those results could be due to the affinity of carnosine to react with sugars, which could negatively influence mitochondrial activity and an oxidative state by decreasing pyruvate production. Hence, in experiment 2, LF samples were treated with a combination of carnosine (0 and 50mM) and pyruvate (0 and 5mM) in a 2x2 factorial arrangement. We observed that samples treated with pyruvate (5mM) had decreased percentage of cells with low mitochondrial activity. On the other hand, carnosine (50mM) increased total motility, progressive motility and fast cells. We also observed a tendency to increased progressive velocity and mitochondrial activity in the combination of treatments. There was no difference on sperm susceptibility to OE between treatments. However, this variable correlated negatively with the percentage of motile and rapid cells as well as those showing intact membrane and acrosome. These results indicate that the byproduct of lipid peroxidation (MDA) may cause damage to DNA, mitochondria and sperm kinetics. In this context, carnosine (100mM) appears to have a mild protective effect on DNA against the accumulation of MDA. Furthermore, 50mM of carnosine seems to improve progressive velocity and mitochondrial activity when associated with pyruvate (5mM). Thus, carnosine and pyruvate can be used on cryoinjuries prevention in low freezeability samples.

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11

Tallon, Mark J. "Carnosine metabolism in human skeletal muscle." Thesis, University of Chichester, 2005. http://eprints.chi.ac.uk/843/.

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12

Ng, W. L. "Carnosine and related peptides in mammalian tissues." Thesis, Swansea University, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.638320.

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Carnosine, homocarnosine and anserine were found to be present in rat quadriceps, gastrocnemius, and pectoral muscles, and in spinal cord and brain. These dipeptides could not be detected in heart, lung, kidney, liver or testes. A method for the determination of carnosine and related compounds, using reverse phase HPLC, has been developed. A novel colorimetric method, based on the formation of a coloured complex with Cobalt (II), was also developed for the determination of carnosine. The distribution of carnosine synthetase and homocarnosine synthetase in rat spinal cord, brain or skeletal muscles was studied. Carnosine synthetase was also shown to be responsible for anserine synthesis. On gel-filtration, carnosine synthetase separates into two active fractions (M_r 250,000 and 120,000). Homocarnosine synthetase has a M_r of 115,000. A requirement by carnosine synthetase for NAD⁺ and glucose was confirmed. Pyridoxal-5-monophosphate effectively replaced the requirement for glucose; a hypothesis is presented to explain this. Ca²⁺ ions were shown to activate carnosine synthetase but not homocarnosine synthetase. Significant effects on carnosine and homocarnosine synthetase from rat brain and gastrocnemius were produced by 5'-AMP, 5'-cAMP, 5'-GMP and 3',5'-cGMP. Carnosine synthetase activity, both from rat brain and from gastrocnemius, was inhibited by α-alanine which was shown to be an alternative substrate to β-alanine resulting in formation of L-α-alanyl-L-histidine. Carnosinase and homocarnosinase were partially purified from brain and from gastrocnemius. Carnosinase has a M_r of 120,000 and 50,000 and was activated by dithioerythritol. Homocarnosinase has a M_r of 54,000. Carnosinase was insensitive to thiol compounds and a range of metal ions. Homocarnosinase was activated by Co^2+ ions and was inhibited by thiol compounds. The K_m for carnosinase and homocarnosinase was found to be 4.0 mM and 1.0 mM, respectively. Carnosine, homocarnosine and anserine were shown to have no effect on hexokinase, phosphofructokinase, α-oxoglutarate, NAD⁺-isocitrate dehydrogenase and pyruvic dehydrogenase.

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13

Bispo, Vanderson da Silva. "Investigação dos mecanismos biológicos de detoxificação de aldeídos α,β- insaturados em ratos SODG93A modelo para ALS." Universidade de São Paulo, 2015. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-07122015-105825/.

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A lipoperoxidação gera diversas espécies carbonílicas altamente reativas dentre as quais se destacam acroleína (ACR), malondialdeído (MDA), 4-hidroxi-2-hexenal (HHE) e 4-hidroxi-2-nonenal (HNE). A principal via endógena de metabolização desses compostos é através de conjugação com glutationa por ação da glutationa-S-tranferase. Contudo, diversos trabalhos têm mostrado que dipeptídeos contendo histidina, tal como a carnosina (CAR), também podem formar conjugados com aldeídos e auxiliar na detoxificação desses compostos. Em nosso trabalho adutos de CAR com ACR, HHE, HHEd5, HNE e HNEd11 foram sintetizados, purificados e caracterizados. A reação da CAR com ACR foi estudada em detalhes. Resultados mostraram que a carnosina reage com acroleína formando 03 produtos principais: m/z = 265, m/z = 283 e m/z = 303, sendo este último mais estável e mais abundante. Dados de RMN H1, COSY e HSQC permitiram elucidar a estrutura dessa molécula (m/z = 303) e propor uma rota de reação. Em seguida, uma metodologia baseada em cromatografia líquida acoplada à espectrometria de massas do tipo \"Ion Trap\" (ESI+ HPLC/MS-MS) foi desenvolvida e validada para quantificação simultânea dos adutos sintetizados. Pelo método desenvolvido é possível quantificar com precisão 25 pmol de CAR-HHE, 1 pmol de CAR-ACR e 1 pmol de CAR-HNE com um coeficiente de variação de aproximadamente 10 % e acurácia de 98 % (HHEd5 e HNEd11 foram usados como padrão interno). Análise em urina de adultos não fumantes mostraram que os produtos sintetizados estão presentes na urina de humanos em concentrações de 3,6 ± 1,4; 2,3 ± 1,5 e 1,3 ± 0,5 nmol / mg de creatinina, respectivamente para CAR-ACR, CAR-HHE e CAR-HNE. Em ratos transgênicos SODG93A modelo para esclerose lateral amiotrófica (ELA), a suplementação da dieta dos animais com 35 ± 5 mg carnosina/animal/semana melhorou a manutenção do peso e a sobrevida dos animais. Análises dos adutos sintetizados em amostras de músculo sugerem que a metabolização de aldeídos esteja comprometida nesses animais e que a carnosina poderia funcionar como \"scavenger\" para esses compostos. Esses resultados comprovam que dipeptídeos de histidina atuam na detoxificação de compostos carbonílicos e participa de suas vias de excreção. Além disso, a caracterização da estrutura e desenvolvimento de método sensível de detecção abre a possibilidade de utilização desses adutos como biomarcadores de estresse redox e exposição a aldeídos.
Lipid peroxidation generates reactive carbonyl species, including 4-hydroxy-2-nonenal (HNE), acrolein (ACR), 4-hydroxy-2-hexenal (HHE) and malondialdehyde (MDA). One major pathway of aldehyde detoxification in vivo is through conjugation with glutathione catalyzed by glutathione-S-transferases or, alternatively, by conjugation with endogenous histidine containing dipeptides, such as carnosine (CAR). The reaction of CAR with ACR was investigated in an effort to assess its possible biological role. One stable adduct was isolated by reverse-phase HPLC and characterized on the basis of extensive spectroscopic measurements. The proposed reaction route for product formation involves the reaction of the CAR amino group with ACR via a Schiff base formation followed by dehydration and cyclization through Michael addition in the imidazole ring forming an instable compound with m/z = 265. The subsequent reaction with another molecule of ACR followed by cyclization gives rise to the final product with m/z = 303.A highly sensitive method involving HPLC-MS analysis was developed for the simultaneous accurate quantification of CAR- ACR, CAR-HHE and CAR-HNE adducts in human urinary samples from non-smoking adults. This methodology permits quantification of 10 pmol CAR-HHE and 1 pmol of CAR-ACR and CAR-HNE. Adduct levels in urine were 3.6 ± 1.4, 2.3 ± 1.5, 1.3 ± 0.5 nmol/mg of creatinine, respectively to CAR-ACR, CAR-HHE and CAR-HNE. In SODG93A transgenic rats model to amyotrophic lateral sclerosis (ALS), the food supplementation of the animals with 35 ± 5 mg carnosine/animal/week improve de body weight and the life span of the ALS treated group. Analysis of the synthesized adducts in muscle sample showed suggest than aldehyde metabolization is compromised in this animals and that may be carnosine work like a scavenger for these compounds. Our results indicate that carnosine adduction can be an important detoxification route of α,β -unsaturated aldehydes. Moreover, carnosine adducts quantification may be useful as redox stress indicator in vivo.

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Dunnett, Mark. "Carnosine metabolism and function in the thoroughbred horse." Thesis, n.p, 1995. http://ethos.bl.uk/.

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Lee, Beom Jun. "Antioxidant Activity of Carnosine and Phytate: Application as Meat Preservatives." DigitalCommons@USU, 1998. https://digitalcommons.usu.edu/etd/5452.

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The antioxidant activity of carnosine and phytic acid was investigated using several model systems. Carnosine and phytic acid alone inhibited metal ion-catalyzed deoxyribose degradation. Carnosine strongly inhibited metal ion-catalyzed lipid peroxidation in liposomes and in ground beef homogenates. Phytic acid facilitated oxidation of Fe (II) to Fe (III), and it inhibited hemeprotein + H202-catalyzed lipid peroxidation in linoleic acid micelles. Antioxidant and color stabilizing effects of carnosine and phytate were investigated in a beef model system. Both compounds increased the rate of pH decline in pre-rigor beef muscle and stabilized fresh meat color by inhibiting metmyoglobin formation and lipid peroxidation in raw samples during storage at 4°C. Both compounds inhibited heme degradation and lipid peroxidation in cooked beef during storage at 4°C. Iron released from heme was strongly related to lipid peroxidation in cooked beef. Ascorbic acid inhibited metmyoglobin formation on the surface of ground beef patties but not in the bulk of the product. In contrast, camosine inhibited metmyoglobin formation and brown color development throughout the product. Carnosine increased cook yield and salt-soluble protein, but ascorbic acid had no effect on cook yield and decreased salt-soluble protein. Carnosine was more effective on inhibition of lipid peroxidation than was ascorbic acid. Phytate greatly enhanced water-holding capacity of raw and cooked meat in a dilute beef model system. Effects of 0.5% sodium phytate, sodium pyrophosphate, and sodium tripolyphosphate, along with 1% NaCl, on physicochemical properties of restructured raw and cooked beef were compared. In raw beef, the treatments with sodium phytate, sodium pyrophosphate, and sodium tripolyphosphate increased meat pH and salt-soluble protein level, and inhibited metmyoglobin formation and lipid peroxidation, compared to the control. In cooked beef, the treatments with sodium phytate, sodium pyrophosphate, and sodium tripolyphosphate increased bind strength, cooked yield, moisture level, and meat pH, and inhibited lipid peroxidation. The treatments with sodium pyrophosphate and sodium tripolyphosphate increased inorganic orthophosphate level in both raw and cooked beef, compared to sodium phytate and the control. These results indicate that carnosine and phytate can be used as meat preservatives for extending shelf-life and enhancing water-holding capacity of meat and meat products.

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Silva, Vinícius da Eira. "Avaliação da espectroscopia de ressonância magnética para quantificação de carnosina muscular em humanos." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5164/tde-27102017-090103/.

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Introdução: A carnosina (beta-Alanil-L-Histidina) é um dipeptídeo encontrado em altas concentrações em diversos tecidos excitáveis, tais como o coração, cérebro e músculo. Embora o número de evidencias sobre os efeitos benéficos da carnosina esteja aumentando, muitos desses estudos apresentam uma importante limitação: a falta de mensuração da carnosina intramuscular. O principal motivo é a necessidade de realização de biópsias musculares. Nesse sentido, um novo método não invasivo baseado na ressonância magnética de hidrogênio (1H RNM) foi apresentado como alternativa. Objetivos: Determinar a reprodutibilidade, acurácia e sensibilidade do 1H MRN na determinação do conteúdo de carnosina muscular em seres humanos contra a referência \"padrão-ouro\" de quantificação de carnosina, cromatografia líquida de alta eficiência (HPLC) em extratos musculares obtidas por biópsia muscular. Métodos: O estudo foi dividido em duas sub-investigações, sendo a primeira delas uma investigação in vitro que testou a linearidade do sinal da carnosina na 1H RMN. Para a segunda investigação dezesseis homens fisicamente ativos (18 - 35 anos) sem doença crônico-degenerativa ou qualquer disfunção no aparelho locomotor se voluntariaram. Os participantes foram submetidos a duas sessões no total. Na sessão inicial, características antropométricas e de composição corporal foram mensuradas, cada indivíduo teve sua concentração de carnosina muscular do gastrocnêmio avaliada através da análise 1H MRN (um teste-reteste foi realizado com uma sub amostra para verificar a reprodutibilidade do método), em seguida uma biópsia muscular do gastrocnêmio foi realizada. Os voluntários então se submeteram a um período de quatro semanas de suplementação de 6,4 g. de beta-alanina por dia, estimulo que comprovadamente aumenta a carnosina muscular, durante esse período também foi realizada uma avaliação nutricional para determinar a quantidade carnosina ingerida em suas dietas. Na segunda sessão os indivíduos mais uma vez tiveram suas composições corporais avaliadas e realizaram o teste de 1H RMN e biópsia muscular para acessar suas concentrações de carnosina muscular. Resultados: In vitro: A linearidade de sinal de 1H RMN para as concentrações de carnosina testadas apresentou valores de R2 de 0,9771. In vivo: O teste-reteste da 1H RMN apresentou coeficiente de variação médio de 9,9 ± 10,34% e coeficiente de correlação interclasse de = 0,775 (95% C.I.: 0,324-0,939). Comparando-se os dois métodos: As concentrações de carnosina (em mmol/kg musculo seco) não foram estatisticamente diferentes tanto no pré (1H RMN -20,8±6,2; HPLC -23,3±10,5; p=0,45; 95% CI= -4,5 -9,6) quanto no pós-suplementação (1H RMN - 35,2±13,2; HPLC-27,8±11,7; p=0,15; 95% CI= -3,5 - 17,8) (n=13). Os valores de delta da concentração de carnosina muscular (em %) também não foram estatisticamente diferentes (1H RMN - 69,7±66,7; HPLC -38,2±58,2 p=0,16; 95% CI= -14,5 -77,5; ES=0,90). Ao observar os dados individuais, nota-se também baixa correlação dos dados individuais entre os métodos (R2 = 0,0448; r =0,212; p= 0,229). Conclusão: A 1H RMN apresentou baixa reprodutibilidade e acurácia quando comparada ao padrão ouro (HPLC), não sendo possível sua utilização para mensuração de carnosina muscular
Introduction: Carnosine (beta-Alanyl-L-Histidine) is a dipeptide found in high-concentrations in human tissue, such as heart, brain and muscle tissue. Although the body of evidence relating beneficial effects of carnosine is increasing, most of these studies have an important limitation: the lack of intramuscular carnosine measurement. The main reason for the absence of this measurement is the method of analysis; a muscle sample must be obtained via a muscle biopsy. In this regard, a new method non-invasive based on hydrogen magnetic resonance (1H NMR) has been used as an alternative. Objectives: The present study aims to determine the reproducibility, accuracy, and sensitivity of H-MRS in the determination of muscle carnosine content in humans; comparative data analysis will be performed against the \"standard\" reference of HPLC carnosine quantification in muscle extracts obtained by muscle biopsy. Methods: The study was divided into two sub-investigations. The first of which was an in vitro investigation that tested the linearity of the carnosine signal at 1 H NMR. For the second investigation, sixteen physically active men (18-35 years) without chronic-degenerative disease or any dysfunction in the locomotor apparatus volunteered. The participants were submitted to 2 sessions in total; Upon arrival to the initial session, anthropometric and body composition characteristics were collected before each individual underwent a muscle carnosine measurement of the gastrocnemius via H-MRS analysis (a test-retest was performed with a sub-sample to verify the reproducibility of the method) followed by a gastrocnemius muscle biopsy. Thereafter volunteers were submitted to a 4-week supplementation period of 6.4 g. of beta-alanine per day, a stimulus proven to increase muscle carnosine, during this period, volunteers had their carnosine dietary ingestion evaluated as well. Following the supplementation period, individuals were subjected to another body composition evaluation, 1H RMN and muscle biopsy. Results: In vitro: The linearity of 1 H NMR signal for carnosine concentrations tested showed R2 values of 0.9771. In vivo: 1 H NMR test-retest showed a mean coefficient of variation of 9.9 ± 10.34% and ICC= 0.775 (95% C.I.: 0.324-0.939).Comparing the methods: Carnosine concentrations (in mmol / kg dry muscle) were not significant difference either the in pre (1 H NMR -20.8 ± 6.2, HPLC -23.3 ± 10, 5, p = 0.45, 95% CI = -4.5 -9.6) and post-supplementation (1 H NMR - 35.2 ± 13.2, HPLC-27.8 ± 11.7, p = 0.15, 95% CI = -3.5-17.8) . The delta values of muscle carnosine concentration (in %) were not statistically different (1 H NMR - 69.7 ± 66.7; HPLC -38.2 ± 58.2 p = 0.16; 95 % CI = -14.5 -77.5; ES = 0.90). Comparing the individual data, there was a low correlation between the methods (R2 = 0.0448, r = 0.212, p = 0.229). Conclusion: 1H NMR showed low reproducibility and accuracy when compared to the gold standard (HPLC), not being possible its use for carnosine quantification

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Matthews, James C. "Absorption of carnosine and methionylglycine by sheep ruminal and omasal epithelia." Thesis, Virginia Tech, 1991. http://hdl.handle.net/10919/41689.

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Carnosine and methionylglycine (using ³⁵S-methionylglycine as a representative marker) absorption and transfer across ruminal and omasal epithelia collected from four (carnosine) and seven (methionylglycine) sheep were studied using parabiotic chambers that were repeatedly sampled over a 240-min incubation. The quantity of dipeptide absorbed or transferred was linearly (P < .01) dependent on substrate concentration. Carnosine was transferred intact across both tissues. More carnosine was absorbed (P < .02) and transferred (P < .01) by the omasal epithelia. Methionylglycine was transferred intact across both tissues, but less (P < .01) remained intact in serosal buffer after 240 min incubation with omasal epithelium than with ruminal epithelium. The amount of methionylglycine that accumulated in each tissue was similar. Methionylglycine accumulation in tissues plus transfer after 240 min was greater (P < .01) for omasal tissue. The ability of sheep ruminal and omasal epithelia to absorb and transfer carnosine and methionylglycine in parabiotic units was demonstrated. Dipeptide translocation across forestomach epithelial tissues, which has not been reported previously, may be an important route for supplying dietary amino acids to the ruminant.
Master of Science

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Lardé, Eva. "Peptides et Cancers : contribution à l'étude de la carnosine, l'asporine et la thrombospondine." Thesis, Sorbonne université, 2019. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2019SORUS520.pdf.

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Le développement de nombreuses maladies comme le cancer, le diabète, les maladies neurodégénératives comme Parkinson et Alzheimer, est associé à un déséquilibre entre la mort cellulaire régulée et la prolifération cellulaire. La propagation des cellules tumorales est corrélée à la mise en place d’un métabolisme énergétique et d’un microenvironnement tumoral qui permettent aux cellules de survivre dans des conditions extrêmes. Elle est également liée à la production d’espèces carbonylées réactives (RCS) durant le stress oxydant, menant à l’inflammation chronique du tissu ainsi qu’à une déficience du système immunitaire. Dans le cadre d’une collaboration entre le Laboratoire des Biomolécules à Paris et le Laboratoire de Recherche sur les Métastases à Liège j’ai contribué au développement de peptides ciblant ces différents traits caractéristiques du cancer. En effet, dans un premier temps, nous avons développé des analogues de la carnosine, un dipeptide endogène visant à capturer les différents RCS qui dégradent les macromolécules de notre organisme et induisent des mutations favorisant la glycolyse aérobie. Dans un deuxième temps, nous avons analysé la conformation d’un peptide de 47 acides aminés issu de l’asporine, un protéoglycane de la matrice extracellulaire, afin de développer des analogues stables qui inhiberaient la prolifération des cellules du cancer du sein triple négatif en se liant au facteur de croissance TGF-β1. Dans une troisième partie, nous avons étudié des peptides agonistes du récepteur CD47, mimant la partie C-terminal de la Thrombospondine-1, de façon à induire sélectivement la mort immunogénique des cellules tumorales. Ces approches sont des stratégies prometteuses qui, combinées à d’autres thérapies, permettraient d’inhiber la croissance tumorale et de limiter les problèmes de rechute rencontrés avec les thérapies actuelles
The development of many diseases such as cancer, diabetes, neurodegenerative diseases, is correlated with the metabolic production of Reactive Carbonyl Species (RCS) and a deficient immune system, leading to the set-up of Warburg effect and the survival of cancer cells in extremes conditions. In this context, a partnership between the laboratoire des biomolecules in Paris and the laboratoire de recherche sur les metastases in Liège was set to design peptide tools targeting these hallmarks. First, we develop carnosine’s analogs, an endogenous dipeptide, in order to stabilize this molecule and to quench RCS that damage our organisms’ macromolecules. Then, we studied the asporin’s conformation, a proteoglycan from the extracellular matrix, in order to develop peptides that will suppress the cellular proliferation of triple negative breast cancer by linking the growth factor TGF-β1. Finally, we studied agonist peptides targeting the CD47 receptor, mimicking the CD47 binding epitope of thrombospondine-1. These peptides trigger selective regulated cell death while sparing normal cells. These strategies might permit to inhibit cellular proliferation and to reduce cancer relapse when combined to other chemotherapies

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Letzien, Ulrike. "Effects of Carnosine and L-histidine on Viability and Expression of Pyruvate Dehydrogenase Kinase 4 in Human Glioblastoma Cells." Doctoral thesis, Universitätsbibliothek Leipzig, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-197285.

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Die Arbeit behandelt die Ergebnisse von Experimenten über die Wirkung des Dipeptides Carnosin (β Alanyl L Histidin) und der Aminosäuren L Histidin und β-Alanin auf Kulturen der humanen Zellreihen U87, T98G und LN405, welche von Zellen des malignen Hirntumors Glioblastoma multiforme abgeleitet sind. Die Vitalität der Zellen nach Inkubation mit Carnosin oder L Histidin wurde anhand der Adenosintriphosphatproduktion und der Dehydrohenaseaktivität für Inkubationszeiträume von 24, 48 und 72 Stunden bestimmt. Dabei zeigte sich eine signifikant niedrigere Vitalität der mit Carnosin oder L Histidin inkubierten Zellen gegenüber der unbehandelten Kontrolle. Dieser Effekt war bei L Histidin stärker ausgeprägt. Bei Messungen der Lakatdehydrogenaseaktivität im Medium der Zellen, welche als Indikator für Zellnekrosen diente, zeigten nur die mit L Histidin inkubierte Zellen Zeichen von Nekrose. Die gleichen Messungen wurden auch an humanen embryonalen Nierenzellen durchgeführt (HEK 293), wobei sich ein ähnliches Ergebnis feststellen ließ. In den drei Zellreihen wurde zudem mittels qRT-PCR die mRNA-Expression für die beiden Enzyme Carnosinase 1 und Carnosinase 2 bestimmt, welche L Histidin von Carnosin abspalten. Im Vergleich mit Proben aus normalem Hirngewebe war die Expression beider Enzyme in den Glioblastomzellen deutlich geringer, wenngleich nachweisbar. Nachdem vorhergehende Studien [8] einen Anstieg der Expression von mRNA der Pyruvatdehydrogenasekinase 4 (PDK4) in mit Carnosin inkubierten Glioblastomzellen gezeigt hatten, wurde dieser Effekt hier auch mittels qRT-PCR in mit L Histidin inkubierten Zellen nachgewiesen. Eine Wirkung von Carnosin oder L Histidin auf ein Reportergen des PDK4-Promoters wurde ebenfalls untersucht, wobei sich kein signifikanter Effekt nachweisen ließ.

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March, Daniel Scott. "Effects of bovine colostrum and zinc carnosine on markers of exercise induced intestinal damage." Thesis, Aberystwyth University, 2014. http://hdl.handle.net/2160/3be67ce6-7e58-4307-a5c9-d2881248551c.

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Maravai, Soliany Grassi. "Efeitos da administração intracerebroventricular de carnosina sobre parâmetros de estresse oxidativo em cérebro de ratos." reponame:Repositório Institucional da UNESC, 2014. http://repositorio.unesc.net/handle/1/3490.

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Dissertação de Mestrado apresentada ao Programa de Pós Graduação em Ciências da Saúde, da Universidade do Extremo Sul Catarinense – UNESC, para obtenção do título de Mestre em Ciências da Saúde.
A carnosina (β-alanina-L-histidina) é um dipeptídeo encontrado em abundância na musculatura esquelética, no músculo cardíaco e no sistema nervoso central. É um composto utilizado como terapia adjuvante para o tratamento de doenças neurodegenerativas associadas ou não ao envelhecimento, devido ao seu conhecido efeito protetor contra oxidantes gerados na fisiopatologia dessas doenças. Entretanto, até o momento, nenhum estudo avaliou o efeito da administração isolada de carnosina sobre parâmetros de estresse oxidativo em cérebro de ratos. Com o intuito de elucidar os efeitos antioxidantes da carnosina, este estudo investigou os efeitos da administração aguda intracerebroventricular (ICV) de carnosina sobre parâmetros de estresse oxidativo em córtex cerebral, cerebelo, hipocampo e estriado de ratos machos com 60 dias de vida. Para tanto, os animais foram submetidos a uma cirurgia estereotáxica com implantação de cânula no ventrículo lateral direito. Três dias após a cirurgia, os animais receberam uma administração única ICV de carnosina (6,4 μmol) através da cânula guia. Os animais do grupo controle receberam 6,4 μmol de NaCl em solução aquosa. Uma hora após a administração, os animais foram eutanasiados por decapitação com guilhotina e as estruturas cerebrais a serem estudadas foram limpas e dissecadas para posteriores análises bioquímicas. Para avaliação da oxidação lipídica e proteica, foram determinados os níveis de substâncias reativas ao ácido tiobarbitúrico (TBA-RS) e o conteúdo de sulfidrilas, respectivamente. Também foram avaliadas as atividades das enzimas antioxidantes catalase (CAT) e superóxido dismutase (SOD) nas mesmas estruturas cerebrais. Observou-se que os níveis de TBA-RS não foram alterados em nenhuma das estruturas cerebrais avaliadas nos animais que receberam carnosina em comparação ao grupo controle. Por outro lado, o conteúdo de grupos sulfidrila encontrou-se aumentado em cerebelo e hipocampo de ratos submetidos à administração de carnosina, sugerindo uma maior proteção conferida aos compostos tiólicos presentes nas células. Em relação às defesas antioxidantes, pôde-se observar um aumento da atividade da CAT em córtex cerebral dos animais que receberam administração ICV de carnosina. Tais resultados corroboram estudos anteriores que demonstram efeitos antioxidantes para a carnosina. Entretanto, a administração ICV deste dipeptídeo ocasionou uma inibição da atividade da SOD em estriado, o que pode ser um efeito tóxico da carnosina. Tomados em conjunto, os resultados do presente estudo demonstram efeitos ambíguos da carnosina sobre parâmetros de estresse oxidativo. Este trabalho corrobora o efeito antioxidante descrito, mas apresenta uma evidência de um possível efeito tóxico exercido pela carnosina. Estudos complementares são necessários para avaliar a segurança do uso terapêutico desta molécula.

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Tanaka, Rosana Aramaki. "Avaliação do efeito radioprotetor da carnosina (Beta- alanil 1- histidina) na reparação tecidual em ratos." [s.n.], 2002. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288936.

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Orientador : Frab Norberto Boscolo
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Mestrado

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Baan, Mieke. "Protective effects of Zinc-L-Carnosine/ Vitamin E on aspirin-induced gastroduodenal injury in dogs." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1242760910.

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Macarini, José Roberto. "Avaliação da toxicidade da carnosina sobre parâmetros de metabolismo energético em músculo esquelético de ratos jovens." reponame:Repositório Institucional da UNESC, 2013. http://repositorio.unesc.net/handle/1/4361.

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Dissertação de Mestrado apresentada ao Programa de Pós-Graduação em Ciências da Saúde, da Universidade do extremo Sul Catarinense, UNESC, para obtenção do título de Mestre em Ciências da Saúde.
Carnosina (β-alanil-L-histidina) é um dipeptídeo composto pelos aminoácidos β-alanina e L-histidina, amplamente distribuído em músculo esquelético de mamíferos. O dipeptídeo é sintetizado por uma ligase, a carnosina sintetase; e é hidrolisado a seus precursores pelas metaloproteases carnosinase sérica e carnosinase citosólica. Níveis séricos elevados de carnosina e dipeptídeos análogos são encontrados em indivíduos com disfunção neurológica e alterações neuromusculares, associadas à deficiência hereditária de carnosinase sérica. No presente trabalho, objetivou-se investigar os efeitos da administração aguda e crônica de carnosina sobre parâmetros do metabolismo energético em músculo esquelético de Wistar machos de 30 dias de vida. Para o experimento agudo, os animais receberam uma dose única do dipeptídeo (100 mg/kg i.p.) e, decorridas 24 horas, foram mortos por decapitação. Já no tratamento crônico, os animais receberam uma dose diária de carnosina (100 mg/kg i.p.) durante 5 dias, e posteriormente foram mortos por decapitação 1 hora após a última injeção intraperitoneal. O músculo esquelético (soleus) foi dissecado e homogeneizado para posterior avaliação da atividade dos complexos I-III, II e II-III da cadeia respiratória e das enzimas sucinato desidrogenase, malato desidrogenase e creatina quinase. Neste estudo, demonstrou-se que, em comparação com o grupo controle, os animais que receberam carnosina agudamente apresentaram uma redução estatisticamente significante da atividade dos complexos I-III e II da cadeia respiratória. Verificou-se também uma tendência de redução, porém não estatisticamente significativa, da atividade do complexo II-III, da malato desidrogenase e da creatina quinase de ratos do grupo carnosina. Por outro lado, em animais administrados cronicamente com o dipeptídeo, observou-se apenas uma tendência de diminuição, embora não estatisticamente significativa, da atividade do complexo I-III do grupo carnosina em comparação com o grupo. Concluindo, a administração aguda de carnosina é capaz de inibir enzimas-chave do metabolismo energético de ratos. É provável que uma disfunção energética secundária ao acúmulo de carnosina possa ajudar a explicar os sintomas neuromusculares observados em pacientes com deficiência de carnosinase sérica, bem como desvendar mecanismos envolvidos na fisiopatologia dessa rara doença.

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Arnould, Jean-Marie. "De la carcirine des crabes à la carnosine des vertébrés : De nouvelles voies métaboliques de l'histamine." Nancy 1, 1987. http://www.theses.fr/1987NAN10126.

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Arnould, Jean-Marie. "De la carcinine des Crabes à la carnosine des Vertébrés de nouvelles voies métaboliques de l'histamine /." Grenoble 2 : ANRT, 1987. http://catalogue.bnf.fr/ark:/12148/cb376023778.

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Oppermann, Henry [Verfasser], Jürgen [Akademischer Betreuer] Meixensberger, Frank [Akademischer Betreuer] Gaunitz, Achim [Gutachter] Aigner, and Ingo [Gutachter] Bechmann. "Untersuchungen zur Regulation des Glucosestoffwechsels in Glioblastomen und dessen Beeinflussung durch Carnosin : Untersuchungen zur Regulation des Glucosestoffwechsels inGlioblastomen und dessen Beeinflussung durch Carnosin / Henry Oppermann ; Gutachter: Achim Aigner, Ingo Bechmann ; Jürgen Meixensberger, Frank Gaunitz." Leipzig : Universitätsbibliothek Leipzig, 2015. http://d-nb.info/1239565275/34.

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Rodriguez-Nino, Maria Angelica [Verfasser], and Benito A. [Akademischer Betreuer] Yard. "Implications of the carnosine-carnosinase system in diabetic nephropathy / Maria Angelica Rodriguez-Nino ; Betreuer: Benito A. Yard." Heidelberg : Universitätsbibliothek Heidelberg, 2020. http://d-nb.info/1223261727/34.

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Rodriguez-Nino, Maria Angelica Verfasser], and Benito A. [Akademischer Betreuer] [Yard. "Implications of the carnosine-carnosinase system in diabetic nephropathy / Maria Angelica Rodriguez-Nino ; Betreuer: Benito A. Yard." Heidelberg : Universitätsbibliothek Heidelberg, 2020. http://nbn-resolving.de/urn:nbn:de:bsz:16-heidok-290999.

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30

Straniero, V. "DESIGN AND SYNTHESIS OF NOVEL BIOACTIVE PEPTIDES AND PEPTIDOMIMETICS." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/217536.

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Nowadays there’s a growing interest in biologically active peptides for the development of new therapeutics; however in some cases, they could not directly use as drugs, due to their inherent limitations, such as rapid metabolism and low oral activity. As a result, peptides are modified into peptidomimetics with specific characteristics, in a rational design. The present PhD project is focused on the synthesis of several peptides and peptidomimetics, structurally different and presenting individual features, properties, targets and pharmaceutical applications. In particular, two are the research studies we’ve developed during the three years, these are the design of novel Carnosine-like derivatives and of new Farnesyl Transferase Inhibitors (FTIs). Concerning the first topic, we investigated how Carnosine (β-alanyl-L-histidine) structural changes influence its role as scavenger of HNE (4-hydroxy-trans-2,3-nonenal) and other toxic aldehydes. For this reason we modified the carnosine structure firstly replacing the Hystidinil- portion with different aromatic system, secondly substituting the β-alanyl portion with ten different amino acids, chosen in order to cover exhaustively the available chemical space. Finally we rigidified the whole structure, inserting a 2-oxazolidinone; the entire compound underwent biological evaluation, testing their ability to quench HNE. As a result, some of the twenty dipeptides showed impressing scavenging activities and great selectivity towards toxic aldehydes, suggesting us that they can represent truly promising candidates for the design of improved carnosine derivatives. Regarding the second subject, we designed, synthesized and tested several peptidomimetics of the CAAX box, where CAAX is the sequence Cysteine-Valine-Isoleucine-Methionine, able to block the farnesylation of RAS proteins and therefore cell proliferation. The design started from a nanomolar range FTI, previously synthesized by our group, where the central dipeptide (AA) is replaced with a 4-amino-2-o-tolylbenzoyl spacer and the Cysteine (C) with the residue 2-amino-4-thiazolylacetyl. The synthesis of the novel FTIs followed two separate approaches; at first we kept the aromatic spacer and modified the N-terminal residue with other heterocycles; the unimproved antiproliferative activity suggested us to apply other kind of modification. Therefore we replaced the o-tolyl with six heteroaromatic residues, in addition the synthesized compounds presented, as N- terminal residue, the 2-amino-4-thiazolylacetyl itself or the 1,4-benzodioxan-2-ylmethyl or the 1,4-benzodioxan-2-ylformyl. In all the three series of compounds, the 2-thienyl, 1-naphtyl and the 3-furanyl derivatives showed the highest FTase inhibition, at low micromolar level. Taken together, our biological activities provide interesting results, confirming that peptides and peptidomimetics should be employed as therapeutics.

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Bortolatto, Guilherme Pedrini [UNESP]. "Efeito da carnosina e da β-alanina no dano produzido pelo exercício intenso no músculo sóleo de ratos." Universidade Estadual Paulista (UNESP), 2015. http://hdl.handle.net/11449/144064.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Intense physical exercise affects the balance between oxidative damage and antioxidant defense in the muscle. Carnosine is a dipeptide composed of the cytoplasmic β-alanine and histidine amino acids. This study aimed to evaluate the effect of carnosine and its β-alanine precursor of oxidative damage caused by intense physical exercise in the soleus muscle of rats. Male Wistar rats weighing between 200 and 240 g were divided into 4 groups: control (sedentary), exercise, exercise + β-alanine and carnosine + exercise. The animal groups submitted to the exercise ran on a treadmill for 60 min to 25 m / min. Factors related to muscle damage and oxidative stress were assessed in blood serum and homogenate of the soleus muscle. The exercise promoted muscle damage, as observed by increased serum activity of enzymes aspartate aminotransferase and creatine kinase, and also induced oxidative stress could be seen by the increased activity of the enzymes glutathione peroxidase and reductase, decreased reduced glutathione concentration and lipid peroxidation in soleus muscle. Only carnosine kept the parameters close to those of the control group. The results indicate that pretreatment with the soleus muscle carnosine protected mice against oxidative damage and consequent damage caused by intense exercise

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32

Bortolatto, Guilherme Pedrini. "Efeito da carnosina e da β-alanina no dano produzido pelo exercício intenso no músculo sóleo de ratos /." Araçatuba, 2015. http://hdl.handle.net/11449/144064.

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Resumo:O exercício físico intenso afeta o balanço entre ataque oxidativo e a defesa antioxidante no músculo. A carnosina é um dipeptídeo citoplasmático composto pelos aminoácidos β-alanina e histidina. O presente trabalho teve o objetivo de avaliar o efeito da carnosina e do seu precursor β-alanina sobre os danos oxidativos causados pelo exercício físico intenso no músculo sóleo de ratos. Ratos Wistar machos pesando entre 200 e 240 g foram divididos em 4 grupos: controle (sedentários), exercício, exercício + β-alanina e exercício + carnosina. Os animais dos grupos submetidos ao exercício correram em esteira por 60 min a 25 m/min. Fatores relacionados ao dano muscular e estresse oxidativo foram avaliados no soro sanguíneo e no homogenato do músculo sóleo. O exercício promoveu lesão muscular, conforme observado pelo aumento da atividade sérica das enzimas aspartato aminotransferase e creatina quinase, e também induziu o estresse oxidativo, observado pelo aumento da atividade das enzimas glutationa peroxidase e redutase, diminuição da concentração de glutationa reduzida e lipoperoxidação, no músculo sóleo. Apenas a carnosina manteve os parâmetros próximos aos do grupo controle. Os resultados indicam que o tratamento prévio com carnosina protegeu o músculo sóleo de ratos contra os danos oxidativos e a consequente lesão provocada pelo exercício físico intenso
Abstract:Intense physical exercise affects the balance between oxidative damage and antioxidant defense in the muscle. Carnosine is a dipeptide composed of the cytoplasmic β-alanine and histidine amino acids. This study aimed to evaluate the effect of carnosine and its β-alanine precursor of oxidative damage caused by intense physical exercise in the soleus muscle of rats. Male Wistar rats weighing between 200 and 240 g were divided into 4 groups: control (sedentary), exercise, exercise + β-alanine and carnosine + exercise. The animal groups submitted to the exercise ran on a treadmill for 60 min to 25 m / min. Factors related to muscle damage and oxidative stress were assessed in blood serum and homogenate of the soleus muscle. The exercise promoted muscle damage, as observed by increased serum activity of enzymes aspartate aminotransferase and creatine kinase, and also induced oxidative stress could be seen by the increased activity of the enzymes glutathione peroxidase and reductase, decreased reduced glutathione concentration and lipid peroxidation in soleus muscle. Only carnosine kept the parameters close to those of the control group. The results indicate that pretreatment with the soleus muscle carnosine protected mice against oxidative damage and consequent damage caused by intense exercise
Orientador:Mario Jefferson Quirino Lousada
coorientador:Fábio Erminio Mingatto
Banca:Andréa Fontes Garcia
Banca:Elisa Helena Giglio Ponsano
Mestre

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Asperger, Ansgar Karl Adam [Verfasser], and n. n. n. [Akademischer Betreuer] n. "Biochemische Untersuchungen zur Wirkung von Carnosin auf das Wachstum humaner Glioblastomzellen / Ansgar Karl Adam Asperger. Gutachter: n.n. n.n." Leipzig : Universitätsbibliothek Leipzig, 2011. http://d-nb.info/1020088435/34.

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Saile, Jana Asisa [Verfasser]. "Untersuchungen zur Expression der murinen Carnosin-Synthase und Etablierung einer Methode zur nicht-radioaktiven Enzymaktivitätsbestimmung / Jana Asisa Saile." Bonn : Universitäts- und Landesbibliothek Bonn, 2016. http://d-nb.info/1143691857/34.

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35

Bermúdez, Mei-Ling. "Carnosine as a Mechanism-based Intervention in the Thy1-aSyn Mouse Model of Parkinson’s Disease: Neurobehavioral, Biochemical, and Bioinformatic Analyses." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1543839362404126.

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Brown, Josephine M. B. S. "Intranasal carnosine protects against alpha-synuclein accumulation in the substantia nigra and motor dysfunction in the Thy1-aSyn mouse model of Parkinson’s disease." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1573571387865684.

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Brisola, Gabriel Motta Pinheiro. "Efeitos da suplementação de β-alanina sobre a potência anaeróbia, habilidade de esforços repetidos e desempenho no polo aquático /." Rio Claro, 2016. http://hdl.handle.net/11449/144686.

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Orientador: Alessandro Moura Zagatto
Banca: Marcelo Papoti
Banca: Guilherme Giannini Artioli
Resumo: O objetivo geral do presente trabalho foi verificar o potencial ergogênico da suplementação por 4 semanas de β-alanina sobre a potência anaeróbia, habilidade de esforços repetidos e desempenho no polo aquático. 22 jogadores de elite do sexo masculino (média±dp: idade = 18±4 anos, peso = 78,5±9,5 kg e altura = 1,79±0,06 m) participaram do estudo, que foi conduzido de modo randomizado, duplo cego e placebo controlado. Os participantes foram divididos em dois grupos (β-alanina e placebo) de 11 atletas cada e foram submetidos a testes específicos (teste de habilidade de esforços repetidos (RSA) e teste máximo de 30s de salto sob o gol (30CJ)) e semi-específicos (teste de 30s máximo em nado atado (30ATADO), teste máximo de 3 minutos (All Out 3min), teste incremental máximo (GXTATADO) e performance de 200m em nado crawl (P200m)) para a modalidade e um jogo simulado para possibilitar o rastreamento das atividades realizadas por meio de filmagem. As avaliações ocorreram pré e após o período de suplementação (4 semanas). Não foram encontrados efeitos significativos de interação entre os grupos para nenhuma variável do presente estudo. No entanto, alguns ligeiros indícios de melhora com a suplementação de β-alanina foram encontrados como: (1) melhora significativa entre os momentos (pré × pós) no número total de sprints durante o jogo simulado de polo aquático; (2) efeito provavelmente benéfico (análise de inferência baseada na magnitude) para o tempo médio, pior tempo e tempo total na... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The overall aim of this study was to investigate the ergogenic effect of 4 weeks β-alanine supplementation on the anaerobic power, ability to performed repeated efforts and performance of water polo. 22 male elite players (mean±SD age = 18±4 years, weight = 78.5±9.5 kg and height = 1.79±0.06 m) participated in the study, which was conducted in order randomized, double blind and placebo controlled. Participants were divided into two groups (β-alanine and placebo) of 11 athletes each and were subjected to specific tests (repeated sprint ability test (RSA) and maximum 30s jump under the goal test (30CJ)) and semi-specific (30s maximal test in tethered swimming (30TS), maximal 3 min effort (AllOut-3min), tethered swimming graded exercise test (GXTTS) and 200m in front crawl (P200m)) for the modality and a simulated game to enable tracking of the activities carried out by video record. Assessments occurred before and after the supplementation period (4 weeks). There were no significant interaction effects between the groups for any variable of this study. However, some slight improvement indications with β-alanine supplementation were found to: (1) significant improvement between moments (pre × post) the total number of sprints during the simulated game water polo; (2) probably beneficial effect (magnitude-based inference analysis) for the mean time, worst time and total time in the first series of the RSA test (RSA1); (3) significant improvement between moments for mean force and integral of force during the 30TS and P200m; (4) significant improvement between moments for peak power at GXTTS. Therefore, it is concluded that supplementation for 4 weeks of β-alanine can promote only slightly improve some parameters related to swimming ability in water polo as total number of sprints in simulated game, mean time,... Complete abstract electronic access below)
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D’Astous-Pagé, Joël. "Implication de la carnosine musculaire chez le porc en croissance dans la détermination des caractères de qualité de la viande et mesure des niveaux d’expression de gènes associés à son métabolisme." Mémoire, Université de Sherbrooke, 2017. http://hdl.handle.net/11143/10486.

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Pour améliorer la compétitivité de l'industrie porcine, le porc canadien doit être attrayant et présenter un avantage unique qui permettrait à cette industrie de se démarquer des autres produits alimentaires. La carnosine pourrait offrir un tel avantage et ainsi aider l'industrie porcine à obtenir une plus grande part de marché, tout en modifiant les perceptions négatives liées à la consommation de viande. La carnosine fut, en 1900, le premier peptide jamais isolé à partir de matériel biologique. Chez l'homme, certaines propriétés curatives ont été associées à la consommation de carnosine. Ces propriétés peuvent être expliquées, en partie, par la capacité de la carnosine à inhiber la glycation non enzymatique des protéines et leurs agrégations au cours du vieillissement. Mais son potentiel d'améliorer la qualité de la viande de porc est tout aussi intéressant à développer. En effet, la carnosine musculaire agirait comme tampon de pH, ce qui permettrait de ralentir l’acidification dans le muscle squelettique. La carnosine présente également des propriétés antioxydantes, ce qui peut aussi contribuer à améliorer la qualité de la viande. Ce projet de maîtrise fait partie d’un programme de recherche plus large ayant pour objectif d'augmenter la teneur en carnosine musculaire chez le porc en croissance afin de différencier et de donner une valeur ajoutée au porc canadien. Dans cette étude, nous avons supposé qu’un contenu élevé en carnosine musculaire serait associé à de meilleurs paramètres de qualité de la viande chez le porc en croissance et que l'expression des gènes liés au métabolisme de la carnosine serait modulée chez les porcs ayant différents niveaux de carnosine musculaire, de même que dans les muscles de porcs de différentes races. En second lieu, nous avons supposé que des polymorphismes d'un seul nucléotide (SNP), observés sur les gènes liés au métabolisme de la carnosine, pourraient aussi affecter le dépôt de carnosine musculaire chez le porc. Un total de 282 porcs de race pure a été utilisé pour ce projet, incluant 85 Duroc, 92 Landrace et 105 Yorkshire, lesquels provenaient de 16 producteurs différents à travers le Canada. Ces porcs sont entrés à la station de Deschambault (Québec, Canada) entre 10 à 16 jours d’âge, ont tous été élevés dans des conditions similaires et abattus à 120 kg de poids vif. Les carcasses ont été suivies individuellement à l’abattoir pour permettre l’échantillonnage du muscle longissimus thoracis immédiatement après la mort de l’animal et de prendre les mesures de qualité de la viande, 24 h postmortem. Les valeurs de qualité de la viande et de carnosine musculaire étaient disponibles au début de ce projet de maîtrise (projet de recherche antérieur). Dans un premier temps, les niveaux d’expression génique de gènes du métabolisme de la carnosine ont été mesurés par la méthode de PCR en temps réel. Les gènes sélectionnés incluent des enzymes (ABAT, 4-aminobutyrate aminotransferase; CARNS1, carnosine synthase 1; CNDP1, CNDP dipeptidase 1; CNDP2, CNDP dipeptidase 2; HDC, histidine decarboxylase) et des transporteurs (SLC6A6, solute carrier family 6, member 6; SLC15A1, solute carrier family 15, member 1; SLC15A2, solute carrier family 15, member 2; SLC15A3, solute carrier family 15, member 3; SLC15A4, solute carrier family 15, member 4; SLC36A1, solute carrier family 36, member 1) reliés au métabolisme de la carnosine. Les gènes ABAT, CDNP1, HDC, SLC15A1 et SLC15A2 ont été abandonnés puisque leurs transcrits étaient indétectables ou présents à de très faibles quantités. En ce qui concerne les autres gènes, l’analyse des résultats a révélé un effet de race pour l’expression génique de CARNS1, CNDP2 et SLC36A1, les valeurs les plus élevées étant observées chez les porcs de race Duroc, lesquels présentent également des niveaux plus élevés en carnosine musculaire. Pour chaque race, les animaux ont été regroupés en trois catégories selon leur teneur en carnosine musculaire (Bas, Moyen et Élevé). Pour les Duroc, l'abondance en ARNm de la CARNS1 est plus élevée pour le groupe Bas que pour les groupes Moyen et Élevé en carnosine. Ce résultat laisse croire à un possible rétrocontrôle de la carnosine musculaire sur la transcription de la CARNS1, l’enzyme responsable de sa synthèse. Pour les gènes SLC15A3 et SLC15A4, nous observons des niveaux d’ARNm plus élevés chez les animaux à haute teneur en carnosine. Ainsi, des niveaux plus élevés de carnosine musculaire pourraient entrainer une augmentation de la transcription de SLC15A3 et SLC15A4, deux gènes impliqués dans le transport de la carnosine. Dans un deuxième temps, l’effet de la quantité de carnosine musculaire sur différents caractères de qualité de la viande a aussi été étudié. Ces résultats nous démontrent que les porcs ayant des niveaux de carnosine élevés, présentent également une meilleure qualité de la viande, tel que démontré par un pH à 24h plus élevé, une meilleure capacité de rétention d’eau et une diminution des indices de couleur b* (couleur jaune) et L* (luminance).Enfin, une recherche de polymorphismes d’ADN a aussi été effectuée sur quatre gènes cibles (CARNS1, SLC6A6, SLC15A3 et SLC15A4) ayant un fort potentiel d’affecter les niveaux de carnosine musculaire. Les séquences codantes et 3’UTR de chacun de ces gènes ont tout d’abord été séquencées sur une population restreinte de 28 Duroc, 27 Landrace et 30 Yorkshire, incluant des porcs présentant de faibles et de hauts niveaux de carnosine musculaire. Un total de 27 SNPs ont été identifiés pour ces quatre gènes. De ce nombre, quatre SNPs furent sélectionnés pour effectuer le génotypage de la population entière (n = 590). De ces SNPs, deux entrainent un changement d’acide aminé dans le gène SLC15A4 (SNP c.658A>G : Ile220Val; SNP c.818G>A : Ser273Asn)) et deux autres SNPs dans le gène SLC15A3 se retrouvent sur un site reconnu par un micro-ARN (c.*35C>T and c.*52C>T). Des analyses d’association ont ensuite été effectuées afin de déterminer l’effet des différents SNPs et diplotypes sur les caractères de qualité de la viande et sur les niveaux de carnosine et d’ansérine (analogue méthylé de la carnosine). Nos résultats démontrent qu’une sélection en faveur du génotype c.658AA ou du diplotype AA/GG pour le gène SLC15A4 résulterait en une augmentation de carnosine musculaire et une amélioration de certains paramètres de qualité de la viande tels que la couleur, la rétention d’eau et le pH à 24 h. Collectivement ces résultats montrent que les porcs présentant de hauts niveaux de carnosine musculaire présentent également une meilleure qualité de la viande. De plus, les niveaux d’expression de certains gènes du métabolisme de la carnosine sont modulés selon la race de porc (influence génétique possible) et aussi selon le contenu de carnosine musculaire. Enfin, une amélioration générale de la qualité de la viande serait possible par la sélection d’allèles favorables du gène SLC15A4. Cependant, les fréquences observées pour les allèles mineures du SNP c.658A>G (i.e. Duroc, 0.01; Landrace, 0.09) suggèrent une amélioration génétique limitée chez les Duroc et les Landrace.

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Cunha, Luiz Antônio da. "Avaliação da influência do dipeptídeo N-ß-alanil-L-histidina (L- carnosina) sobre a cinética de expansão de culturas de células diplóides humanas, estirpe MRC-5." Instituto de Tecnologia em Imunobiológicos, 2007. https://www.arca.fiocruz.br/handle/icict/5812.

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Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
Um acordo internacional de transferência de tecnologia, firmado em 2003, entre a FIOCRUZ e a GlaxoSmithKline permitiu o acesso de Bio-Manguinhos a um moderno processo produtivo da vacina tríplice viral (TVV) contra o sarampo, a caxumba e a rubéola. A produção dessa vacina é parte do compromisso de Bio-Manguinhos com o programa nacional de auto-suficiência em imunobiológicos, tido como uma meta prioritária da política de saúde pública do governobrasileiro. A tecnologia aplicada para a produção da TVV envolve o uso de células MRC-5 como substrato celular para a produção de vírus vacinais da rubéola, particularmente da cepa Wistar RA27/3. A estirpe MRC-5 é reconhecida como um dos mais importantes substratos celulares para a produção de vacinas virais, e também tem sido adotada como modelo de estudo para senescência celular in vitro. A senescência celular é um estágio fisiológico complexo pelo qual, invariavelmente, qualquer população de células somáticas normais passa após atingir um determinado número de mitoses. Esseestágio fisiológico é caracterizado nas células diplóides pela contenção da capacidade de se multiplicar e pelo desenvolvimento de alterações morfológicas peculiares, especialmente quando cultivadas in vitro. Com o objetivo de aprimorar omonitoramento de estirpes de células diplóides humanas (HDCS – do inglês Human Diplóide Cells Strains) e contribuir para o estabelecimento da base de conhecimento necessário para a futura aplicação no processo de produção de TVV em Bio-Manguinhos, nós avaliamos culturas de células MRC-5 condicionadas com carnosina, em três diferentes aspectos: cinética de crescimento, propagação da cepa vacinal, Wistar RA27/3, do vírus da rubéola e a expressão do marcador biológico de senescência, a enzima β-galactosidase AS (β-gal AS). A avaliação do potencial antioxidante e antisenescente atribuído a carnosina, um dipeptídeo ubíquo à fisiologia de todos os animais superiores, sobre as células MRC-5 pode contribuir para aprimorar os procedimentos de qualificação e controle de células diplóides associados à produção de vacinas, e aindaservir para o desenvolvimento de novos produtos e a pesquisa científica. Aspectos dacinética de crescimento da cultura de células condicionadas com carnosina, observados neste estudo, são discutidos sob o ponto de vista da teoria do compromisso celular com a senescência. Todas as culturas de células MRC-5 avaliadas demonstraram a expressão da β-gal AS através do uso de X-Gal ou ONPG como substrato. Não encontramos variações no perfil de propagação de cepas vacinais do vírus da rubéola que possam ser associadas ao condicionamento das células MRC-5 com carnosina, nas condições testadas.
An international technology transfer agreement established between FIOCRUZ and GlaxoSmithKline in 2003, will provide Bio-Manguinhos with access to a modern manufacturing process for the production of the triple viral vaccine against measles, mumps and rubella (TVV). The production of TVV forms part of the Bio-Manguinhos commitment to the self-sufficiency national programin immunobiologicals, within the Brazilian government public health prioritized policies. The TVV technology employs diploid cells derived from normal human lung tissue(MRC-5) as the substrate for production of the attenuated rubella vaccine virus,Wistar RA27/3. The MRC-5 strain is one of the most important cellular substrates for viral vaccine manufacturing and in addition is widely used as a model for in vitrostudies of cell senescence. Cellular senescence is a physiological stage which normal somatic cells beyond certain duplication level go through, invariably. Such physiological stage is characterized by growth arrest and specific morphological changes, commonly, observed in diploid cells under in vitroculture environment. Aiming to contribute with the human diploid cells strains (HDCS) monitoring study and line up with the establishment of the necessaryknowledge base for the conduction of the TVV production process in Bio-Manguinhos, weevaluated MRC-5 cell cultures conditioned with carnosine under three different aspects: growth kinetics, propagation of the attenuated strain of rubella virus Wistar RA27/3 and the expression of the senescence bio-marker, SA β-Galactosidase. An evaluation of the antioxidant and antisenescence features attributed to carnosine, a dipeptide, ubiquitous to the physiology of all superior animals, over MRC-5 may contribute to the improvement of the qualification and control procedures in production of vaccines, product development and scientific research. Aspects of the growth kineticsof MRC-5 cells conditioned with carnosine observed in this study are discussed in relation to the cellular commitment theory. All MRC-5 tested demonstrated SA β-Galactosidase activity, as verified by enzyme processing of X-Gal or ONPG used as substrate. Additionally, no variations in the propagation profile of the attenuated rubella virus by treating cells with carnosine could be characterized in this study.

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Letzien, Ulrike [Verfasser], Jürgen [Akademischer Betreuer] Meixensberger, Frank [Akademischer Betreuer] Gaunitz, Florian [Gutachter] Lordick, and Achim [Gutachter] Aigner. "Effects of Carnosine and L-histidine on Viability and Expression of Pyruvate Dehydrogenase Kinase 4 in Human Glioblastoma Cells / Ulrike Letzien ; Gutachter: Florian Lordick, Achim Aigner ; Jürgen Meixensberger, Frank Gaunitz." Leipzig : Universitätsbibliothek Leipzig, 2016. http://d-nb.info/1240395663/34.

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Fredriksson, Benjamin. "Effekt av ß-alanintillskott på Muskelkarnosin, Blodlaktat och Fysisk prestation. : En Litteraturstudie med Meta-analys." Thesis, Linnéuniversitetet, Institutionen för kemi och biomedicin (KOB), 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-89384.

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Bakgrund: Användningen av kosttillskott har ökat de senaste åren. Detta leder till att det kontinuerligt produceras nya tillskott som inte har någon evidens för effekt. Ett kosttillskott som har fått ökat intresse de senaste åren är ß-alanin. För aktiviteter där glykolys stimuleras och mjölksyraproduktionen är hög har ß-alanin föreslagits vara ett effektivt tillskott. ß-alanins effekter och funktioner i kroppen är inte helt fastställda. Syfte: Syftet med denna studie var att analysera ß-alanintillskotts effekter på muskelkarnosinkoncentrationen, blodlaktat, muskelstyrka och uthållighet/tid till utmattning. Metod: Studien är utformad som en systematisk litteraturstudie med meta-analys. Pubmed användes som databas för litteratursökningen. Meta-analyser utfördes för karnosinkoncentration och blodlaktat. Resultat: Dosering med 3.2g/dag av ß-alanin under 4 veckor visar signifikanta effekter på karnosinkoncentrationen. Effektstorleken på karnosinkoncetration mellan grupperna var 1.255 (p = 0.001) efter 4 veckor av supplementering. Effektstorleken mellan grupperna för 10 veckor var 2.054 (p=0.008). Inga signifikanta effekter på blodlaktat, effektstorleken mellan grupperna var 0.148 (p=0.278). Signifikant effekt av ß-alanin på tid till utmattning (TTE) vid hög-intensitets cykling. ß-alanintillskott visade signifikant effekt på en repetition max (1RM) och helkroppsstyrka (WBS). Slutsats: ß-alanintillskott med en dosering på minst 3.2g/dag i 4 veckor ger en signifikant ökning av muskelkarnosinkoncentrationen. Större dosering än 3.2g visar inte på större effekt. ß-alanin har inte någon signifikant effekt på blodlaktat. Signifikant effekt visades på TTE för hög-intensitetscykling/sprinter. ß-alanintillskotts effekt på muskelstyrka är svår identifierad eftersom det bara var två studier som kunde inkluderas.
Background: The use of dietary supplements has increased in recent years. Which leads to the continuous production of new supplements that have no evidence of effect. A dietary supplement that has gained increased interest in recent years is β-alanine. For activities where glycolysis is stimulated and lactic acid production is high, β-alanine has been suggested to be an effective supplement. The effects and functions of ß-alanine in the body are not fully established. Purpose: The purpose of this study was to analyze the effects of ß-alanine supplementation on muscle carnosine concentration, blood lactate, muscle strength and endurance/time to exhaustion. Method: The study is designed as a systematic literature study with meta-analysis. Pubmed was used as a database for the literature search. Meta-assays were performed for carnosine concentration and blood lactate. Result: Dosage at 3.2g / day of β-alanine for 4 weeks shows significant effects on carnosine concentration. The size of the effect on carnosine concentration between the groups after 4 weeks of supplementation was 1,255 (p = 0.001). The effect size between the groups for 8-10 weeks was 2,054 (p = 0.008). No significant effects on blood lactate, the effect size between the groups was 0.148 (p = 0.278). Significant effect of βalanine on time to fatigue (TTE) in high intensity cycling. β-alanine supplementation showed significant effects on a repetition max (1RM) and whole body strength (WBS). 2 Conclusion: β-alanine supplementation with a dosage of at least 3.2g / day for 4 weeks gives a significant increase in muscle carnosine concentration. Larger dosages than 3.2g does not show greater effect. β-alanine does not have a significant effect on blood lactate. Significant effect was shown on TTE for high intensity cycling sprints. The ßalanine supplemental effect on muscle strength is difficult to identify because only two studies could be included.

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Zhu, Xiaochun. "Characterization of Protein Modification by Products of Lipid Peroxidation." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1225734704.

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Garzon, D. "HIGH RESOLUTION MASS SPECTROMETRIC STRATEGIES FOR DETECTION OF PROTEINS AND PEPTIDES COVALENTLY MODIFIED BY ELECTROPHILIC XENOBIOTICS AND ENDOGENOUS INTERMEDIATES." Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/250677.

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Non enzymatic protein covalent modifications are involved in the toxic effects induced by electrophilic xenobiotics as well as by endogenous cytotoxic oxidation by-products. Aim of my Ph.D work was to set-up MS methods for the identification, characterization and quantification of non-enzymatic covalently modified proteins and peptides in biological matrices. To reach this goal both tandem MS and high resolution approaches were employed due to the wealth of structural and molecular information that these techniques can provide. As a first step the MS methods were applied for understanding in both in vitro and ex vivo conditions the mechanism of protein haptenation induced by amoxicillin (AX). The MS approach was then focused to study in ex vivo condition the covalent reaction between histidine dipeptides, such as carnosine, and toxic endogenous intermediates like reactive carbonyl species (RCS). .

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Oppermann, Henry. "Untersuchungen zur Regulation des Glucosestoffwechsels in Glioblastomen und dessen Beeinflussung durch Carnosin: Untersuchungen zur Regulation des Glucosestoffwechsels inGlioblastomen und dessen Beeinflussung durch Carnosin." Doctoral thesis, 2014. https://ul.qucosa.de/id/qucosa%3A13264.

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Das Glioblastoma multiforme (GBM) ist der am häufigsten vorkommende maligne Hirntumor mit äußerst ungünstiger Prognose für die betroffenen Patienten. Typisch für die Tumore ist eine hohe Aktivität der Glykolyse zur Generierung von ATP und zur Bereitstellung von Makromolekülen für die Zellproliferation, während die oxidative Phosphorylierung auch in Gegenwart von Sauerstoff praktisch keine Bedeutung für die Generation von ATP hat, was auch als Warburg Effekt bekannt ist. Das natürlich vorkommende Carnosin (β-Alanyl-LHistidin) wirkt sich antiproliferativ auf Tumorzellen aus, was mit einer Inhibition der glykolytischen ATP Produktion einhergeht. Der Mechanismus der Inhibition ist weitgehend unverstanden und ist Gegenstand der vorliegenden Arbeit. Im Rahmen der durchgeführten Arbeit wurde der Einfluss von Carnosin auf die mRNA Expressionen von für die Glykolyse relevanten Genen untersucht, wobei eine starke Induktion der Pyruvatdehydrogenase Kinase (PDK) 4 in drei GBM Zelllinien beobachtet wurde. Weiterhin konnte gezeigt werden, dass L-Histidin den gleichen Effekt wie Carnosin zeigt, nicht jedoch β-Alanin, L-Alanin oder L-Alanyl-L-Histidin. Da Tumorzellen die intrazelluläre Gewebscarnosinase aber kaum die extrazelluläre Serumcarnosinase exprimieren, liegt die Vermutung nahe, dass die antineoplastische Wirkung des Carnosins auf die enzymatische Spaltung von Carnosin und die daraus resultierende Freisetzung von L-Histidin zurückzuführen ist. In weiteren Untersuchungen wurden Hinweise erbracht, dass Carnosin durch eine Beeinflussung von Histon-Deacetylasen, die endogene PDK4 mRNA Expression steigern könnte. Zusätzlich wurden die Proteinexpressionen der PDK1 und 4 unter dem Einfluss von Carnosin untersucht.

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Asperger, Ansgar Karl Adam. "Biochemische Untersuchungen zur Wirkung von Carnosin auf das Wachstum humaner Glioblastomzellen." Doctoral thesis, 2010. https://ul.qucosa.de/id/qucosa%3A11135.

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Das Glioblastom ist mit 70 % aller Gliome der häufigste humane Hirntumor mit sehr ungünstiger Prognose. Es konnte gezeigt werden, dass das natürlich vorkommende Dipeptid Carnosin (β-Alanyl-L-histidin) die Proliferation von Glioblastomzellen inhibiert. Diese Wirkung des Carnosins konnte ebenfalls in vivo nachgewiesen werden. Da Carnosin auch einen Einfluss auf den ATP-Haushalt der Glioblastomzellen besitzt, war das Ziel dieser Arbeit einen Wirkungsort von Carnosin zu identifizieren, womit die ATP mindernden und proliferationshemmenden Eigenschaften erklärt werden können. Es wurde untersucht, ob Carnosin den Energiemetabolismus der Glioblastome beeinflusst. Dabei konnte mithilfe zellbiochemischer Methoden gezeigt werden, dass die untersuchten Zelllinien nicht von der Energieversorgung durch die mitochondriale oxidative Phosphorylierung abhängen, da sich weder Hemmung (KCN) noch Entkopplung (DNP) der Elektronentransportkette auf den zellulären ATP-Gehalt auswirkten. Carnosin hingegen verringerte den ATP-Spiegel dieser Zellen. Die Hemmung der Glykolyse durch Oxamat (LDH-Hemmung), bewirkte einen starken Abfall des intrazellulären ATP-Spiegels, worauf Carnosin keinen zusätzlichen Effekt mehr besaß. Carnosin konnte eine Wirkung auf die glykolytische ATP-Synthese zugesprochen werden. Da ein direkter, molekularer Wirkungsort auf diesem Weg nicht identifiziert werden konnte, wurde parallel untersucht, ob sich über Proteomanalysen der Glioblastomzelllinie T98G ein Wirkungsort, bzw. -mechanismus bestimmen lässt. Anhand der Methode der zweidimensionalen Gelelektrophorese (2D-GE) konnten 31 signifikant differenziell exprimierte Proteine detektiert werden, von denen 6 Proteine (VBP-1, OLA-1, TALDO 1, UROD, BAG-2, GRPEL1) über MALDI-TOF-Analysen identifiziert wurden. In Western-Blot-Analysen konnte ein Protein (VBP-1), neben T98G, auch in primären Glioblastomzelllinien als differenziell exprimiert nachgewiesen werden. Anhand der zellbiologischen und proteinbiochemischen Untersuchungen konnte einerseits eine Verbindung des Carnosins zum HIF1α-Signalweg und andererseits zur generellen posttranslationalen Peptidprozessierung hergestellt werden. Der direkte Nachweis eines Einflusses von Carnosin auf HIF1α wurde aber bisher nicht erbracht.

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Oppermann, Henry. "Pre-clinical investigation of carnosine’s anti-neoplastic effect on glioblastoma: uptake, signal transduction, gene expression and tumour cell metabolism." 2019. https://ul.qucosa.de/id/qucosa%3A72167.

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Das Glioblastom ist der häufigste maligne Tumor des zentralen Nervensystems. Trotz leitliniengerechter Therapie, bestehend aus mikrochirurgischer Resektion, Strahlentherapie und ergänzender Chemotherapie mit Temozolomid, beträgt die 2-Jahres-Überlebensrate nur ca. 17%. Daher sind dringend neue Therapieansätze erforderlich. Dem natürlich vorkommenden Dipeptid Carnosin, welches vor über 100 Jahren erstmals isoliert wurde, konnten viele physiologische Funktionen zugeschrieben werden. Zu Beginn unserer Arbeiten war bekannt, dass das Dipeptid das Wachstum von Krebszellen inhibiert, wobei die genauen Mechanismen der antineoplastischen Wirkungsweise weitgehend unbekannt waren. Die Untersuchungen im Rahmen der vorliegenden Habilitationsarbeit setzten sich mit möglichen Wirkmechanismen des Dipeptides auseinander, wobei ebenfalls Fragestellungen zur klinischen Anwendung von Carnosin bearbeitet wurden. Im ersten Abschnitt werden die Transportmechanismen von Carnosin in Glioblastom-Zellen beschrieben. Weiterhin wird die Frage beantwortet, ob das Dipeptid die biologisch aktive Verbindung ist oder ob L-Histidin von Carnosin abgespalten werden muss, um die antineoplastische Wirkung zu entfalten. Der zweite Abschnitt beschäftigt sich mit den Einflüssen von Carnosin auf die Signaltransduktion und Genexpression. Im dritten Abschnitt wird unter anderem mit einem Metabolomics-Ansatz der Stoffwechsel von Glioblastom-Zellen charakterisiert und der Einfluss von Carnosin auf diesen bestimmt. Im vierten Abschnitt wird ein neuartiges Ko-Kultur Modell zur Untersuchung von Carnosins Einfluss auf Glioblastom-Zell-Migration und Koloniebildung vorgestellt. Weiterhin untersuchten wir die möglichen Interaktionen des Dipeptides mit der Standardtherapie von Glioblastomen. Zusammenfassend zeigten wir, dass Carnosin durch drei verschiedene Transporter aufgenommen werden kann. Das Dipeptid hemmt sowohl Proliferation und Migration von Glioblastom-Zellen. Die Spaltung des Dipeptides ist für seine antineoplastische Wirkung nicht notwendig. In die Zelle aufgenommen, wirkt Carnosin inhibitorisch auf den Pentosephosphatweg. Eine mögliche Erklärung dafür lieferte die beobachte nicht-enzymatische Reaktion von Glycerinaldehyd-3-phosphat mit dem Dipeptid. Weiterhin zeigten unsere Experimente zum ersten Mal eine Carnosin-bedingte Veränderung der Histonacetylierung und eine damit einhergehende Beeinflussung der Genexpression. Da das Dipeptid den Effekt der Radio-/Chemotherapie verstärkt, sollte die Wirkung von Carnosin in einer klinischen Studie an Glioblastom-Patienten untersucht werden.
Glioblastoma is the most common malignant tumour of the central nervous system. Only ~17% of patients undergoing standard therapy, including microsurgical resection, radiotherapy and adjuvant chemotherapy using temozolomide survive two years after diagnosis. Hence, new therapeutic approaches are urgently needed. The naturally occurring dipeptide carnosine was discovered more than 100 years ago. Since then, many physiological functions and beneficial effects have been ascribed to it. Previous studies demonstrated that carnosine inhibits growth of cancer cells. However, at the beginning of our investigations were the mechanisms behind carnosine’s anti-neoplastic effect mostly unknown. The present work addresses possible modes of action of carnosine and issues regarding the clinical application of the dipeptide. In the first paragraph we describe the transport mechanisms of carnosine in glioblastoma cells. Furthermore, we deal with the problem whether carnosine is the biological active compound or release of L-histidine from the dipeptide is required to deploy its anti-neoplastic effect. The second paragraph addresses the influence of carnosine on glioblastoma cell signal transduction and gene expression. In the third paragraph we characterise the metabolism of glioblastoma cells and how it is influenced by carnosine by using a metabolomics approach. The fourth paragraph introduces a novel co-culture model which allows the analysis of carnosine’s impact on glioblastoma cell migration and colony formation. Furthermore, the possible interaction of the dipeptide with the glioblastoma standard therapy is investigated. In conclusion, we demonstrated that three different transporters are capable for the uptake of carnosine in glioblastoma cells. The dipeptide inhibited in addition to proliferation also migration of glioblastoma cells. Moreover, cleavage of carnosine was not required for its anti-neoplastic effect. After taken up by the cell, carnosine inhibits the pentose phosphate pathway. The observed non-enzymatic reaction of glyceraldehyde-3-phosphate with the dipeptide could possibly explain this effect. Furthermore, our experiments showed for the first time that carnosine influences gene expression by an effect on histone acetylation. As the administration of carnosine arguments the effects of radio-/chemotherapy, we encourage the clinical evaluation of the dipeptide for glioblastoma patients.

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47

Yen, Wen-Yen, and 顏文妍. "In vitro assessment of immunomodulating bioactivity of carnosine." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/45181655552794607505.

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Abstract:

碩士
國立臺灣海洋大學
食品科學系
92
Carnosine（b-alanyl-L-histidine；CAR）is present in the nervous system of different classes of vertebrates. This peptide is synthesized by the enzyme CAR synthetase. In vitro, this substance acts as antioxidant, free radical scavenger, physiological buffer, radioprotectant, and metal ion chelating agent. The present study, assessment the effect of CAR and its component, b-Alanine (Ala) and L-histidine (His), which possesses immunomodulatory activity in Vitro. Oxdative stress was induced by incubation with a free radical generator, AAPH. The result suggested that CAR and its component have no effect of cell lines (10 mM). 75 mM CAR decrease NBT reduction ratio by scavenge O2- . 5 mM CAR can promote the phagocytose of PBMC；5 mM AAPH induce DNA fragmentation of cell lines (HL-60, THP-1) and decrease cell viability. Cellas were treated with AAPH for 12 h then add CAR for 4 h have no effect of cell viability,but add 2 mM CAR at the same time could increased cell viability by MTT test；CAR (2 and 5 mM) were decrease apoptosis used the cell cycle determination.AAPH was ROS inducer, our results presumed that the protection of CAR was decreased the ROS production and increased cell viability.

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48

Meng-hsiao and 林孟曉. "Histidine and Carnosine delay diabetic deterioration in mice." Thesis, 2005. http://ndltd.ncl.edu.tw/handle/97298363156643059312.

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Abstract:

碩士
中山醫學大學
營養學研究所
93
In vivo effects of histidine amd carnosine against diabetes deterioration in diabetic Balb/cA mice were studied. Histidine and carnosine at 0.5, 1 g/l were added into drinking water. After 4 weeks intake of these agents, the content of histidine and carnosine in plasma, heart and liver significantly elevated (p<0.05). The intake of these agents significantly decreased plasma glucose and fibronectin levels (p<0.05); however, only 1 g/l histidine and carnosine treatments significantly increased insulin level (p<0.05) in diabetic mice. Triglyceride level in heart and liver was dose-dependently reduced by histidine or carnosine treatments (p<0.05); however, only 1 g/l histidine and carnosine treatments significantly reduced cholesterol level in heart and liver (p<0.05). The administration of histidine or carnosine significantly enhanced catalase activity and decreased lipid oxidation levels in kidney and liver (p<0.05); however, only 1 g/l histidine and carnosine treatments significantly increased glutathione peroxidase activity (p<0.05). The increased interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in diabetic mice were significantly suppressed by the intake of histidine or carnosine (p<0.05). These data suggest that histidine and carnosine are potential multiple-protective agents for diabetic complications prevention or therapy.

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49

Lai, Ying-Chen, and 賴穎珍. "Extraction and Antioxidative Activity of Carnosine from Poultry Meat." Thesis, 1997. http://ndltd.ncl.edu.tw/handle/71942244868598847954.

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Abstract:

碩士
東海大學
食品科學系
86
The objective of this research is to produce chicken, duck and turkey meat extract which was high in carnosine and low in iron. The contents ofmoisture, carnosine, free iron, total iron and phosphate of meat extract were analyzed. Antioxidant effectiveness was measured by adding meat extractto the ground pork containing 30 % fat and 2.0 % NaCl that was packaged with PE film and stored at 0℃ for 0, 3, 6 and 9 days. At each storage interval, thiobarbituric acid (TBA) values, total plate counts (TPC) andpH value of ground pork were determined. The percentage of moisture, carnosine, free iron, total iron and phosphateof meat extract increased after concentration. Demineralization reduced the content of carnosine, free iron and total iron but increased the contentof phosphate in meat extract. the breast meat extract had higher carnosine content than the leg meat extract. The content of free iron and total iron was higher in leg meat extract when comparing to that in the breast meatextract. The chicken meat extract contained higher amount of carnosine; and the duck meat extract contained higher amount of free iron and total iron. The groups added with undemineralized chicken breast meat extract had lower TBA values than the control. The higher percentage of meat extract added, the lower TBA values in ground pork resulted. Ground pork added with the concentrated chicken breast meat extract (undemineralization) had lower TBAvalues than the control. However the freeze-dried chicken breast muscle extract promoted the oxidation of ground pork and increased TBA values. The demineralizedchicken breast meat extract could reduce the TBA values of ground pork during storage. The higher concentration of meat extract added, the lower TBA values in ground pork resulted. After freeze-drying, the chicken breast meat extract(with demineralization) had higher content of iron which promoted the oxidation of ground pork. Demineralization could reduce iron content and inctease theconcentration of phosphate and pH value of meat extract. The antioxidant abilityof demineralized meat extract was better than that of the undemineralized meatextract. Ground pork added with undemineralized of demineralized chicken legmeat extracts had lower TBA values than the control. The concentrated and freeze-dried meat extract increased the TBA value of ground pork during storage. The undemineralized chicken meat extract (undried) increased the total platecounts (TPC) of ground pork during storage. The TPC of ground pork increased with the addition of higher concentration of meat extract. The differences in TPCbetween the concentrated and freeze-dried groups were not significant. Ground pork added with demineralizated chicken breast meat extract had lower TPC thanthose added with undemineralizated meat extract. The TPC of ground pork increased with the addition of undemineralized or demineralized meat extract (undried, concentrated and freeze-dried). Especially, the undemineralized meat extract would significantly increased the TPC of ground pork. The pHvalue of pork was not affected by the addition of undemineralizedchicken breast or leg meat extract during storage. However, the pHvalue was affected by the addition of demineralized meat extract. Ground pork added with concentrated or freeze-dried undemineralized chicken breast or leg meat extracthad higher pH value than the control.-1 -aExtraction and Antioxidative Activity of Carnosine from Poultry Meat

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50

KUO, HSIN-YING, and 郭欣穎. "Preventive potential of carnosine on colon carcinogenesis in mice." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/q2dqp8.

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