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KUO, MING-WEN. "ROLE OF N-ACETYL CYSTEINE IN PREVENTING AGE-RELATED HEARING LOSS." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172356377.
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Karalija, Amar. "Diagnostic and therapeutic strategies following spinal cord and brachial plexus injuries." Doctoral thesis, Umeå universitet, Anatomi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-127519.
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Traumatic injuries to the spinal cord and brachial plexus induce a significant inflammatory response in the nervous tissue with progressive degeneration of neurons and glial cells, and cause considerable physical and mental suffering in affected patients. This thesis investigates the effects of the antioxidants N-acetyl-cysteine (NAC) and acetyl-L- carnitine (ALC) on the survival of motoneurons in the brainstem and spinal cord, the expression of pro-apoptotic and pro-inflammatory cell markers, axonal sprouting and glial cell reactions after spinal hemisection in adult rats. In addition, a novel MRI protocol has been developed to analyse the extent of neuronal degeneration in the spinal cord. Rubrospinal neurons and tibial motoneurons were pre-labelled with the fluorescent tracer Fast Blue one week before cervical C3 or lumbar L5 spinal cord hemisection. The intrathecal treatment with the antioxidants NAC (2.4mg/day) or ALC (0.9 mg/day) was initiated immediately after injury using Alzet2002 osmotic mini pumps. Spinal cord injury increased the expression of apoptotic cell markers BAX and caspase 3, induced significant degeneration of rubrospinal neurons and spinal motoneurons with associated decrease in immunoreactivity for microtubule-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker glial fibrillary acidic protein and microglial markers OX42 and ED1 was markedly increased. Treatment with NAC and ALC attenuated levels of BAX, caspase 3, OX42 and ED1 expression after 2 weeks postoperatively. After 4-8 weeks of continuous intratheca ltreatment, NAC and ALC rescued approximately half of the rubrospinal neurons and spinal motoneurons destined to die, promoted axonal sprouting, restored the density of MAP2 and synaptophysin immunoreactivity and reduced the microglial reaction. However, antioxidant therapy did not affect the reactive astrocytes in the trauma zone. The inflammation modulating properties of ALC were also studied using cultures of human microglial cells. ALC increased the microglial production of interleukin IL-6 and BDNF, thereby possibly mediating the anti-inflammatory and pro-regenerative effects shown in vivo. To study degeneration in the spinal cord following pre-ganglionic and post-ganglionic brachial plexus injuries, adult rat models of ventral root avulsion and peripheral nerve injury were used. A novel MRI protocol was employed and the images were compared to morphological changes found in histological preparations. Ventral root avulsion caused degeneration of dendritic branches and axonal terminals in the spinal cord, followed by significant shrinkage of the ventral horn. Extensive astroglial and microglial reactions were detected in the histological preparations. Peripheral nerve injury reduced the density of dendritic branches but did not cause shrinkage of the ventral horn. Quantitative analysis of MRI images demonstrated changes in the ventral horn following ventral root avulsion only, thus validating the developed MRI technique as a possible tool for the differentiation of pre-ganglionic and post-ganglionic nerve injuries.
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Cheng, Huiwen. "Effects of N-acetyl-L-cysteine and Nitric Oxide-releasing Nonsteroidal Anti-Inflammatory Drugs on Breast Cancer and Melanoma Cell Adhesion." Ohio University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1384948906.
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Moore, Thomas B. "The Role of N-acetyl-L-Cysteine (NAC) as an Adjuvant to Opioid Treatment in Patients with Inadequately Controlled Chronic Neuropathic Pain." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4315.
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Introduction. While opioid medications are commonly prescribed for management of neuropathic pain (NP), long-term use has been associated with increased risk for overdose, drug interactions and addiction. New strategies are necessary to better manage chronic pain, thereby reducing need for opioid medications and their associated adverse consequences. N-acetyl-L-cysteine (NAC), an over-the-counter supplement, has shown promise in the treatment of psychiatric and addictive disorders. In addition, NAC has shown promise for reducing physiological signs of NP in laboratory rat models, prompting this study.
Purpose. The present study was an open-label clinical trial of NAC as an adjuvant to opioid treatment for poorly controlled, chronic NP. It examined whether 1200 mg NAC twice daily for 4 weeks was associated with: lower ratings of patient-reported pain; reductions in PRN opioid medication for breakthrough pain; and improvements in physical and mental health quality of life (QoL). The study also examined whether appraisal of pain impacts response to medication.
Method. Participants were N=28 chronic NP patients who consented to study participation. This consisted of 2 baseline assessments, 4 weeks of NAC and 1 post-trial follow-up visit. The majority (N=17) dropped out or were excluded during baseline. Of the remaining participants, N = 11 started the study medication and N=10 completed the study, with daily recordings of pain severity ratings and use of PRN opioid medication. Small sample size limited analyses to qualitative case reviews and effect sizes.
Results. Over 90% of participants receiving NAC completed the study. Case review found varied results. While 4 of 10 participants showed decrease in average pain ratings during NAC, estimated effect sizes for the whole sample were small, bordering on negligible (ω² from .003 to .027) as were those for PRN opioids (Partial Eta-Squared=.0003). Effect size for mental health QoL was medium (Cohen's d=.421).
Conclusions. With N=10, findings must be interpreted with caution. Nonetheless, the study found some albeit small evidence supporting NAC for improving mental health QoL and pain ratings. Several participants reported improvements in pain and mental health domains while taking NAC. NAC was well tolerated with minimal side effects. Lessons from this study will inform design and implementation of future NAC studies.
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Realini, Giulia. "N-acetyl-L-cysteine ethyl ester (NACET) as a potential therapeutic strategy for the prevention and treatment of Age-related Macular Degeneration." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1203143.
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Age-related macular degeneration (AMD) is a multifactorial progressive chronic ocular disease. Genetics, environmental insults, and age-related issues are risk factors for the development of the disease. Dysfunction of retinal pigment epithelium (RPE) is involved in AMD and oxidative stress in RPE is one of the major causes of the etiopathogenesis of AMD. Therefore, the introduction of antioxidants may represent one of the most effective ways to delay the onset of AMD. Glutathione (GSH) is a key player in the detoxification of xenobiotics, their metabolites and of reactive oxygen species (ROS) and consequently many drugs are currently in use as GSH enhancers. N-acetyl-L-cysteine ethyl ester (NACET) is a lipophilic and cell permeable GSH prodrug that has been proposed to delay AMD progression. Here, we reported an RNA-seq transcriptome analysis of human Retinal Pigment Epithelial cells (ARPE-19) and described for the first time that NACET induces transcriptional activation of nuclear factor erythroid 2-related factor 2 (NRF2) target genes. NRF2 is a transcription factor that allows the maintenance of redox homeostasis by binding to the antioxidant responsive elements (ARE) in the upstream promoter region of many antioxidative genes and thereby inducing their transcription. By means of HPLC analysis, RT-qPCR, Western blot analysis, CRISPR-Cas9 gene editing and luciferase assay, we validated the transcriptome analysis and demonstrated that NACET increases the intracellular level of free cysteine and promotes transcriptional activation of NRF2 target genes through inhibition of NRF2 degradation. Moreover, using transcriptional profiling of retina of young and old mice orally treated with NACET, we showed that NACET rescued 57 genes impaired by aging, many of which have been correlated with retinal dysfunctions. Our study suggests that NACET, as cysteine and GSH precursor and as NRF2 activator, may be a useful tool for the treatment of oxidative stress-related retinal diseases. Although we tested NACET focusing on AMD, we also verified that NACET-induced NRF2 activation is not cell-context dependent, suggesting that NACET may be a promising agent for prevention/treatment of any pathology where oxidative stress is involved.
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Schenatto, Ricardo Olimpio. "Uso da N-acetil-L-cisteína no resfriamento de sêmen equino." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2017. http://hdl.handle.net/10183/181359.
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Este estudo teve como objetivo avaliar o efeito da N-acetil-L-cisteína (NAC), adicionada ao diluente composto de leite em pó desnatado, sobre a viabilidade espermática e o estresse oxidativo do sêmen equino resfriado a 5°C. Ejaculados de 8 pôneis da raça Brasileira foram coletados em triplicata resultando em 24 ejaculados. O sêmen foi distribuído em 4 grupos: Equidil® + 0,00 mM (controle), 0,5 mM, 1,0 mM ou 2,5 mM de NAC. As amostras foram armazenadas em tubos de 15mL e mantidas em caixas de transporte de sêmen BotuFLEX® (Botupharma, Botucatu-SP, Brasil). Parâmetros como motilidade total (MT), motilidade progressiva (MP), vigor, pH, resposta ao teste hiposmótico (HOST) e atividade mitocondrial (MTT) foram avaliados nas 24 e 48 h, bem como no sêmen fresco, após a diluição. O vigor, MT e MP foram também avaliados após teste de termorresistência (TTR), na ausência e presença de peróxido. A MT, a MP, o vigor espermático e a MTT foram similares (P > 0.05) entre as concentrações de NAC, nas 24 e 48 h. A resposta ao HOST foi semelhante entre as concentrações de NAC (P > 0,05) nas 24 h de resfriamento, porém nas 48 h ocorreu diminuição da funcionalidade da membrana no grupo NAC 2,5 mM em comparação ao grupo EQUIDIL, sem adição de NAC. A MT, a MP e vigor, das amostras resfriadas por 24 h e submetidas ao TTR, diferiu entre sem e com peróxido (P < 0,05) nos grupos Equidil, 0,5 mM e 1,0 mM, mas foi similar na concentração de 2,5 mM de NAC. Quando o sêmen foi resfriado por 48 h, houve diferença no vigor e MT entre amostras com e sem peróxido (P < 0,05), em todos os grupos testados, mas a MP foi similar entre amostras com e sem peróxido, na concentração 2,5 mM. O pH do diluente Equidil® foi o maior e os grupos Equidil + 0,5 mM e 1,0 mM tiveram valores intermediários, enquanto a concentração de 2,5 mM de NAC gerou valores mais baixos, nos três momentos avaliados (P < 0,05). Não houve variação significativa de pH entre os momentos 0 e 24 h (P= 0,7075) e entre 0 e 48 h (P= 0,4617), em todos os grupos testados. As concentrações de NAC testadas não melhoraram a motilidade, integridade da membrana plasmática, atividade mitocondrial e resposta ao HOST de espermatozoides equinos resfriados a 5°C e armazenados por 48 h. Após TTR, as concentrações de NAC testadas não evitaram a diminuição da motilidade e vigor espermático, na presença de peróxido.<br>The aim of this study was to evaluate the effect of N-acetyl-L-cysteine (NAC) based on skim milk powder extender on sperm viability and oxidative stress of equine semen cooled to 5°C. Ejaculate of 8 ponies of the Brazilian breed were collected in triplicate, resulting in 24 ejaculates, distributed in 4 groups: Equidil® extender + 0.00mm (control), 0.5mM, 1.0mM and 2.5mM of NAC with the semen samples were The samples were stored in 15mL tubes and kept in BotuFLEX® semen transport boxes (Botupharm, Botucatu/SP/Brazil). Parameters, such as motility, vigor, pH, osmolarity, HOST, and MTT were evaluated at 24 and 48 h of cooling also in fresh semen. Vigor, total (TM) and progressive motility (PM) were also evaluated after thermoresistance test (TTR), in the absence and presence of peroxide. TM, PM, sperm vigor and MTT were similar (P > 0.05) between NAC concentrations at 24 and 48 h. The response to HOST was similar between NAC concentrations (P > 0.05) at 24 h cooling, but at 48 h there was a decreased in membrane functionality in 2.5mM NAC group compared to the EQUIDIL group. TM, PM, and vigor of the samples cooled by 24 h and submitted to TTR differed between without and with peroxide (P< 0.05) in the EQUIDIL, 0.5mM and 1.0mM groups, but was similar in 2.5mM NAC. After cooling for 48 h, there was difference in vigor and TM between samples with and without peroxide (P < 0.05) in all groups tested, but the PM was similar between samples with and without peroxide at concentration 2.5mM of NAC. The pH of the EQUIDIL extender was higher and the EQUIDIL + 0.5mM and 1.0mM groups had intermediate values, while the 2.5mM NAC concentration generated lower values in the three evaluated periods (P < 0.05). There was no significant variation of pH between 0 and 24 h (P=0.7075) and between 0 and 48 h (P=0.4617) in all groups tested. The concentrations of NAC tested did not improve motility, plasma membrane integrity, mitochondrial activity and response to HOST equine spermatozoa cooled to 5°C and stored for 48 h. After TTR, the concentrations of NAC tested did not prevent the decrease of motility and sperm vigor in the presence of peroxide.
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Kerksick, Chad M. Willoughby Darryn Scott. "Effects of prophylactic supplementation of N-acetyl-cysteine and epigallocatechin gallate on markers of oxidative stress, inflammation and apoptosis after eccentric contraction-induced injury in untrained males." Waco, Tex. : Baylor University, 2006. http://hdl.handle.net/2104/4881.
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Nocentini, Benedetta. "Indagine su reazioni di sulfa-Michael di interesse in campo cosmetologico e sul trattamento ricostruttore del capello." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2018. http://amslaurea.unibo.it/15849/.
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The aim of this work was to evaluate the reactivity of cysteinyl residues that can be found in damaged human hair with Michael acceptors under mild conditions and to gain information on the hair modifications occurring in hair bleached and then repaired with some commercial formulations. In some patents, the use of some molecules effective for repairing damaged hair is claimed. Their structure is compatible with the occurrence of Michael addition reactions, and the need of more detailed studies about the reaction mechanism and the effect on human hair of commercial products containing hair rebuilding agents has inspired this study. First, the investigation was focused to find Michael acceptors alternative to those claimed by the examined patents. As model reaction N-acetyl-L-cysteine was chosen as nucleophilic agent and different electrophiles, such as quinone- and maleic acid- derivatives, as well as a,b-unsatured ketones and esters were used. Subsequently we investigated, through Raman/IR spectroscopy and electronic scanning microscopy (SEM), on the effect of hair treatment with Michael acceptors studied in the first part and also some commercial hair rebuilding formulations.
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Barbanera, Pedro Octavio. "Estudo do efeito do N-acetil-cisteína através do metabolismo energético, complexos respiratórios e estresse oxidativo no tecido hepático de ratos submetidos ao glutamato monossódico." Botucatu, 2018. http://hdl.handle.net/11449/158323.
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Orientador: Ana Angélica Henrique Fernandes<br>Resumo: A obesidade é considerada um dos maiores problemas de saúde pública em muitos países, uma vez que está associada queda da qualidade de vida. Embora existam vários fatores que corroboram com o desenvolvimento para tal fato, os hábitos alimentares seja o fator relevante. Os transtornos metabólicos podem resultar em alterações na funcionalidade do fígado, podendo desenvolver Doença Hepática Gordurosa Não Alcoólica (DHGNA). Como o número de obesos e as co-morbidades associadas ao sobrepeso vêm aumentando abruptamente nas últimas décadas, vários modelos de obesidade experimental têm sido propostos para investigar os distúrbios metabólicos envolvendo suas causas e consequências. O glutamato monossódico é amplamente utilizado na culinária e também por indústrias alimentícias, contudo atua no sistema nervoso central e promove a degeneração de áreas importantes do hipotálamo que leva a distúrbios da saciedade e, consequentemente acúmulo excessivo de gordura abdominal. Com a finalidade de estudar substâncias que apresentem potencial atividade terapêutica no controle dos distúrbios metabólicos, o N-acetil-cisteína possui propriedades antioxidantes e exerce hepatoproteção. Desta forma, o objetivo do presente estudo foi evidenciar a indução da obesidade pelo glutamato monossódico e determinar o efeito do N-acetil-cisteína sobre os parâmetros calorimétricos, metabolismo energético, atividade dos complexos respiratórios e estresse oxidativo no tecido hepático. Foram utilizados 32 ratos Wins... (Resumo completo, clicar acesso eletrônico abaixo)<br>Abstract: Obesity is considered one of the greatest public health problems in many countries, since it is associated with a drop in quality of life. Although there are several factors corroborating with the development for this fact, eating habits are the relevant factor. Metabolic disorders can result in changes in liver function, and can develop Non-Alcoholic Fatty Liver Disease (NAFLD). As the number of obese and co-morbidities associated with overweight have increased steeply in recent decades, several models of experimental obesity have been proposed to investigate metabolic disorders involving their causes and consequences. Monosodium glutamate is widely used in cooking and also in food industries, but it acts on the central nervous system and promotes the degeneration of important areas of the hypothalamus which leads to satiety disorders and consequently excessive accumulation of abdominal fat. In order to study substances that present potential therapeutic activity in the control of metabolic disorders, N-acetyl-cysteine has antioxidant properties and exerts hepatoprotection. Thus, the objective of the present study was to evidence the induction of obesity by monosodium glutamate and to determine the effect of Nacetyl-cysteine on calorimetric parameters, energy metabolism, respiratory complex activity and oxidative stress in hepatic tissue. Thirty-two Winstar male mice were used at 21 days of age. Initially the animals were distributed in two experimental groups (n = 16). Grou... (Complete abstract click electronic access below)<br>Doutor
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Ibrahim, Marwa Awad Abdel Hamid [Verfasser]. "Immunohistochemical studies of the influence of alkylating substances on the wound healing process and the possible protective role of N-Acetyl Cysteine and Alpha-Linolenic Acid / Marwa Awad Abdel Hamid Ibrahim." Köln : Deutsche Zentralbibliothek für Medizin, 2012. http://d-nb.info/1030211507/34.
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Muranaka, Lígia Segatto. "Mecanismos envolvidos com a sobrevivência de Xylella fastidiosa em condições de estresse e efeito de N-Acetil-L-Cisteína em seu biofilme." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316427.
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Orientadores: Alessandra Alves de Souza, Marco Aurélio Takita<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-16T03:21:51Z (GMT). No. of bitstreams: 1
Muranaka_LigiaSegatto_M.pdf: 4670725 bytes, checksum: f903ecd21649fe431b36cd1ea62d804b (MD5)
Previous issue date: 2010<br>Resumo: Xylella fastidiosa é uma bactéria Gram-negativa que causa várias doenças em diferentes espécies de plantas, como a clorose variegada dos citros (CVC) em Citrus sinensis, cujos danos econômicos são da ordem de milhões de dólares anuais. O desenvolvimento dos sintomas tem sido associado ao bloqueio dos vasos do xilema causado pela formação de um biofilme pela bactéria. Recentemente foi verificado que o biofilme de X. fastidiosa é mais resistente a compostos antimicrobianos que a forma planctônica. Essa resistência tem se mostrado um fenômeno complexo que não pode ser explicado por um único mecanismo, e sim por multifatores. Nesse sentido, a proposta desse trabalho foi identificar, por microarranjos de DNA, genes possivelmente associados à adaptação do biofilme na presença de compostos antimicrobianos, em concentrações letais para células em crescimento planctônico, mas que não inibiram o crescimento do biofilme. Foram encontrados 223 (7,87%) CDS induzidas na presença de cobre e 150 (5,29%) reprimidas. Com tetraciclina foram 450 (15,89%) induzidas e 449 (15,85%) reprimidas. Muitas sequências codificadoras envolvidas com funções da síntese proteica, metabolismo energético, divisão celular e movimentação foram moduladas negativamente em ambas as situações, sugerindo que tais modificações contribuiriam para um provável estado de resistência. Com a adição da dose subinibitória de cobre também foi observada a indução de genes relacionados à adesão e produção de toxinas, que estão envolvidos com a virulência da bactéria em planta, o que sugere esta seria aumentada possivelmente induzindo maior severidade de sintomas. Já com tetraciclina o oposto foi observado, repressão de genes relacionados à formação do biofilme e produção de toxinas. No entanto, identificamos a indução de um possível mecanismo de resposta SOS, pela qual genes relacionados ao sistema toxina-antitoxina seriam superexpressos. Esse sistema provavelmente está envolvido com a morte celular programada e formação de células persistentes. Assim é possível concluir que doses subinibitórias de compostos antimicrobianos poderiam ao invés de matar, induzir a virulência da bactéria, como ocorrido com o cobre, ou a formação de células persistentes, como observado com a tetraciclina. Outra abordagem desse trabalho foi à realização de experimentos in vitro e in vivo com um análogo de cisteína, o N-acetyl-L-cysteina (NAC), que já vem sendo utilizado na medicina para desestruturação de biofilmes de bactériaspatógenas de humanos. Resultados da quantificação da massa celular, número de célulasviáveis e exopolissacarídeos totais revelaram que todas as doses de NAC (1, 2 e 6 mg/mL) testadas nos experimentos in vitro diminuiram a formação do biofilme e inibiram o crescimento de X. fastidiosa, o que indica um possível efeito tóxico dessa substância. Nos experimentos in vivo foi observada uma grande redução dos sintomas de CVC em plantas de C. sinensis infectadas e tratadas com diferentes doses de NAC. Esses estudos abrem uma real perspectiva ao uso dessa substância para o manejo da CVC.<br>Abstract: Xylella fastidiosa is a Gram-negative bacterium that causes several diseases in different plant species, including citrus variegated chlorosis (CVC) in sweet orange (Citrus sinensis L. Osbeck), whose economic damage is of millions of dollars annually. The symptoms development has been associated with the blockage of xylem vessels caused by bacterial biofilm formation. Recently it was found that the biofilm of X. fastidiosa is more resistant to antimicrobial compounds than the planktonic cells. This resistance has been considered as a complex phenomenon that cannot be explained by a single mechanism, but by multi-factors. Accordingly, the intent of this study was to identify through DNA microarray technology, genes possibly involved in adaptation of biofilm cells to the presence of antimicrobial compounds in concentrations that are lethal to cells in planktonic growth, but do not inhibit the cell growth in biofilm. We found 223 (7.87%) genes induced in presence of copper and 150 (5.29%) genes repressed. For tetracycline, there were 450 (15.89%) induced genes and 449 (15.85%) repressed ones. Many genes encoding proteins related to protein synthesis, energy metabolism and cell division were negatively modulated in both, copper and tetracycline treatments, suggesting that these changes could contribute to a state of resistance. When a subinhibitory dose of copper was applied we could also observe the induction of genes related to adhesion and thus biofilm formation and toxin production, suggesting that the bacterial virulence should be increased. The opposite was found for tetracycline. However, we observed the induction of a possible SOS response mechanism in which genes related to a toxin-antitoxin system was overexpressed. This system is probably involved with programmed cell death and formation of persistent cells. We then concluded that subinhibitory doses of antimicrobial compounds could induce bacterial virulence as occurred for copper, or the formation of persistent cells, as observed for tetracycline rather than kill the cells. Another approach of this work was to carry out experiments in vitro and in vivo with an analogue of cysteine, N-acetyl-L-cysteine (NAC), which has been already used in medicine as a drug for disruption of biofilms formed by human pathogenic bacteria. Results of cellular mass quantification, number of viable cells and total exopolysaccharide content revealed that all doses (1.0, 2.0 and 6.0 mg / mL) of NAC tested in in vitro experiments decreased the biofilm formation and inhibited growth of X. fastidiosa, which indicated that this substance could also be toxic for the bacteria. In vivo experiments showed a strong reduction in CVC symptoms in C. sinensis plants infected and treated with different doses of NAC. These studies open a real prospect for the use of this compound in CVC management.<br>Mestrado<br>Genetica de Microorganismos<br>Mestre em Genética e Biologia Molecular
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Möller, Marisa. "Behavioural, neurochemical, inflammatory and mitichondrial markers following social isolation rearing in rats before and after selected deug intervention / Marisa Möller." Thesis, North-West University, 2012. http://hdl.handle.net/10394/9524.
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Purpose:
Schizophrenia is a progressive degenerative illness that has been causally linked to mitochondrial dysfunction, oxidative stress and a pro-inflammatory state. Social isolation rearing (SIR) in rats models the neurodevelopmental aspects of schizophrenia. The antioxidant and glutamate modulator, N-acetyl cysteine (NAC), has demonstrated therapeutic potential in schizophrenia as adjunctive treatment, although this has not been tested in the SIR model. The purpose of this study was to assess whether SIR induces changes in mitochondrial function (adenosine triphosphate (ATP)), pro- vs. anti-inflammatory cytokine balance, tryptophan metabolism, a disturbance in cortico-striatal monoamines and related metabolites, and associated alterations in behaviors akin to schizophrenia, viz. social interaction, object recognition memory and prepulse inhibition (PPI). Moreover, I evaluated whether these bio-behavioral alterations could be reversed with sub-chronic clozapine, or NAC, and whether NAC may bolster the response to clozapine treatment.
Methods: The objectives of the study were pursued through separately conducted studies. Male Sprague-Dawley (SD) rats (10 rats/group) were used in this study (Ethics number: NWU-0035-08-S5). Rats were randomly allocated to either social rearing or SIR for 8 weeks receiving either no treatment, vehicle, NAC (150 mg/kg/day), clozapine (5 mg/kg/day) or a combination of clozapine + NAC (CLZ + NAC) during the last 11 or 14 days of social rearing or SIR. After the 8 weeks, rats were tested for social interactive behaviors, object recognition memory and prepulse inhibition (PPI). Peripheral tryptophan metabolites (determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)) and pro- and anti-inflammatory cytokines (IL-4, IL-6, TNF-α, IFN-γ) (enzyme-linked immunosorbent assay (ELISA)) were determined. Cortico-striatal ATP (bioluminescence assay) and monoamines (high performance liquid chromatography (HPLC)) were also determined.
Results:
SIR-induced significant deficits in social interactive behaviours, object recognition memory and PPI, associated with increased peripheral kynurenine, quinolinic acid (QA), and pro-inflammatory cytokines, as well as a decrease in kynurenic acid (KYNA), neuroprotective ratio and anti-inflammatory cytokines. I also observed an increase in striatal, but reduced frontal cortical ATP, dopamine, serotonin as well as their metabolites and noradrenaline’s metabolite, with noradrenaline increased in both brain regions in SIR rats. A separate dose-response study of NAC (50, 150, 250 mg/kg/day) found 150 mg/kg to be the most appropriate dose for the NAC and CLZ + NAC studies. Clozapine, NAC as well as CLZ + NAC reversed all these changes, with NAC being less effective than CLZ alone. CLZ + NAC was found to be more effective than clozapine alone in reversing certain bio-behavioral alterations induced by SIR. In addition NAC alone dose dependently reversed most of the SIR induced alterations.
Conclusion:
SIR induces behavioral alterations, a pro-inflammatory state, mitochondrial dysfunction and cortico-striatal monoamine alterations, closely resembling evidence in schizophrenia. Importantly, all these bio-behavioral alterations were reversed with clozapine, NAC and CLZ + NAC treatment. However, CLZ + NAC was more effective than clozapine alone in reversing some bio-behavioral alterations, supporting the therapeutic application of NAC as adjunctive treatment in schizophrenia. In addition, NAC dose dependently reversed SIR-induced cortico-striatal serotonin, noradrenaline and metabolites, emphasizing NAC’s potential use in other anxiety and stress- related disorders.<br>Thesis (PhD (Pharmacology))--North-West University, Potchefstroom Campus, 2013
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Schroeder, Ilka Elizma. "A mechanistic study of organochlorine hepatotoxicity." Diss., University of Pretoria, 2011. http://hdl.handle.net/2263/24882.
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Pentachlorophenol, (PCP) is an organochlorine compound which was first developed in the 1930’s. PCP is said to be the most toxic of the chlorophenols and is classified as a hazardous substance and a probable human carcinogen. PCP has proven to be cytotoxic to a number of cell lines translating to its effect on various organs. The aim of the study was to assess organochlorine-induced hepatotoxicity in a mechanistic manner using an in-house developed procedure. Also, the possible hepatoprotective effect of methanolic extracts of the bark of two medicinal plants, Burkea africana (BA) and Syzygium cordatum (SC), as well as the known hepatoprotective agent, N-acetyl cysteine (NAC), were investigated. In addition to PCP, two of its major metabolites, tetrachloro-1,2-hydroquinone (TCHQ) and tetrachloro-1,4-benzoquinone (TCBQ) were also evaluated. A hepatocarcinoma cell line (HepG2) was used to investigate the effect of these compounds on different parameters of cellular function. Cytotoxicity was assessed using the neutral red uptake assay. Cytochrome P4501A1 (CYP1A1) activity was determined using ethoxy-resorufin-O-deethylation as surrogate. Generation of reactive oxygen species (ROS) was investigated by measuring dichlorofluorescein diacetate cleavage. Effects on mitochondrial membrane potential were determined using JC-1 staining, whilst necrosis was investigated by assessing plasma membrane integrity using propidium iodide (PI)staining. The degree of apoptotic death was determined by quantifying caspase-3 activity. Assays were repeated with an additional 1 h pre-treatment of the cells with either NAC, SC or BA in order to investigate whether these compounds were able to protect against the toxicity induced by PCP and its metabolites. The IC50 values of PCP, TCHQ and TCBQ were 68.0, 144.0 and 129.4 μM, respectively. All three test compounds induced CYP1A1 activity with PCP being the most potent. TCBQ produced extensive ROS generation. TCHQ also induced ROS generation, whilst PCP appeared to have no significant effect on ROS generation. All test compounds caused mitochondrial depolarization. None of the test compounds caused an increase in necrotic cell death. PCP, TCHQ and TCBQ had negligible effects on apoptosis. Both SC and BA alleviated the toxic effects observed in cells treated with PCP. Minor increases in viability occurred in cells pre-treated with plant extracts prior to exposure to both metabolites. NAC, as well as both plant extracts, greatly reduced CYP 1A1 activity induced by PCP. NAC, SC and BA exacerbated CYP1A1 induction in cells exposed to concentrations of TCBQ and TCHQ that initially produced little or no effect on CYP1A1 activity. Contrarily, decreased CYP1A1 activity was observed in cells exposed to concentrations of TCBQ and TCHQ where extensive induction of CYP1A1 occurred. NAC, as well as both plant extracts, suppressed ROS generation in cells exposed to all test compounds. In cells exposed to PCP and TCBQ more extensive mitochondrial depolarization was seen when pre-treated with NAC and plant extracts than when exposed to the compounds alone. Negligible effects were seen in pre-treated cells exposed to TCHQ. BA and SC caused increases in necrotic death in cells exposed to the test compounds. NAC, BA and SC had negligible effects on the changes in caspase-3 activity induced by the test compounds. From the results it is proposed that PCP induces its own metabolism by increasing CYP1A1 activity. It also causes mitochondrial insult which could lead to the opening of the mitochondrial permeability transition pore and subsequent release of cytochrome C, activation of caspases and eventually apoptotic cell death. With regard to TCHQ and TCBQ, results suggest that extensive ROS generation caused damage to various cellular macromolecules and that this could be the main cause of their toxicity. NAC, SC and BA appeared to alleviate toxicity in certain instances. Further investigation is required in order to assess them as possible hepatoprotective agents. Copyright<br>Dissertation (MSc)--University of Pretoria, 2011.<br>Pharmacology<br>unrestricted
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McKay, Hart Andrew. "Sensory neuronal protection & improving regeneration after peripheral nerve injury." Doctoral thesis, Umeå universitet, Handkirurgi, 2003. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-52.
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Peripheral nerve trauma is a common cause of considerable functional morbidity, and healthcare expenditure. Particularly in the ~15% of injuries unsuitable for primary repair, standard clinical management results in inadequate sensory restitution in the majority of cases, despite the rigorous application of complex microsurgical techniques. This can largely be explained by the failure of surgical management to adequately address the neurobiological hurdles to optimal regeneration. Most significant of these is the extensive sensory neuronal death that follows injury, and which is accompanied by a reduction in the regenerative potential of axotomised neurons, and in the supportive capacity of the Schwann cell population if nerve repair is delayed. The present study aimed to accurately delineate the timecourse of neuronal death, in order to identify a therapeutic window during which clinically applicable neuroprotective strategies might be adopted. It then proceeded to investigate means to increase the regenerative capacity of chronically axotomised neurons, and to augment the Schwann cells’ ability to promote that regenerative effort. Unilateral sciatic nerve transection in the rat was the model used, initially assessing neuronal death within the L4&5 dorsal root ganglia by a combination of morphology, TdT uptake nick-end labelling (TUNEL), and statistically unbiased estimation of neuronal loss using the stereological optical disector technique. Having identified 2 weeks, and 2 months post-axotomy as the most biologically relevant timepoints to study, the effect upon neuronal death of systemic treatment with acetyl-L-carnitine (ALCAR 10, or 50mg/kg/day) or N-acetyl-cysteine (NAC 30, or 150mg/kg/day) was determined. A model of secondary nerve repair was then adopted; either 2 or 4 months after unilateral sciatic nerve division, 1cm gap repairs were performed using either reversed isografts, or poly-3-hydroxybutyrate (PHB) conduits containing an alginate-fibronectin hydrogel. Six weeks later nerve regeneration and the Schwann cell population were quantified by digital image analysis of frozen section immunohistochemistry. Sensory neuronal death begins within 24 hours of injury, but takes 1 week to translate into significant neuronal loss. The rate of neuronal death peaks 2 weeks after injury, and neuronal loss is essentially complete by 2 months post-axotomy. Nerve repair is incompletely neuroprotective, but the earlier it is performed the greater the benefit. Two clinically safe pharmaceutical agents, ALCAR & NAC, were found to virtually eliminate sensory neuronal death after peripheral nerve transection. ALCAR also enhanced nerve regeneration independently of its neuroprotective role. Plain PHB conduits were found to be technically simple to use, and supported some regeneration, but were not adequate in themselves. Leukaemia inhibitory factor enhanced nerve regeneration, though cultured autologous Schwann cells (SC’s) were somewhat more effective. Both were relatively more efficacious after a 4 month delay in nerve repair. The most profuse regeneration was found with recombinant glial growth factor (rhGGF-2) in repairs performed 2 months after axotomy, with results that were arguably better than were obtained with nerve grafts. A similar conclusion can be drawn from the result found using both rhGGF-2 and SC’s in PHB conduits 4 months after axotomy. In summary, these findings reinforce the significance of sensory neuronal death in peripheral nerve trauma, and the possibility of its` limitation by early nerve repair. Two agents for the adjuvant therapy of such injuries were identified, that can virtually eliminate neuronal death, and enhance regeneration. Elements in the creation of a bioartificial nerve conduit to replace, or surpass autologous nerve graft for secondary nerve repair are presented.
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Selvin, David. "Regulation of Myoplasmic Ca2+ During Fatigue in KATP Channel Deficient FDB Muscle Fibres." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/26174.
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It is known that muscles that lack KATP channel activity generate much greater unstimulated [Ca2+]i and force than normal muscles during fatigue. The increase in unstimulated force in KATP channel deficient muscles is abolished by a partial inhibition of L-type Ca2+ channels, suggesting that it is due to a Ca2+ influx through L-type Ca2+ channels and a subsequent increased myoplasmic Ca2+. However, there is also evidence that the increase in resting force is abolished by NAC, a ROS scavenger. The objective of this study was to reconcile these observations by studying the hypothesis that “the increase in resting [Ca2+]i during fatigue in KATP channel deficient muscles starts with an excess Ca2+ influx through L-type Ca2+ channels, followed by an excess ROS production that causes a further increase in resting [Ca2+]i”. To test the hypothesis, single FDB fibres were fatigued with one tetanic contraction/sec for 180 sec. KATP channel deficient fibres were obtained i) by exposing wild type muscle fibers to glibenclamide, a KATP channel blocker and ii) by using fibres from Kir6.2-/- mice, which are null mice for the Kir6.2 gene that encodes for the protein forming the channel pore. Verapamil, a L-type Ca2+ channel blocker, applied at 1 μM, significantly reduced resting [Ca2+]i during fatigue in glibenclamide-exposed wild type fibres. NAC (1 mM) also reduced resting [Ca2+]i in glibenclamide-exposed muscles. The results suggest that the increase in resting [Ca2+]i during fatigue in KATP channel deficient FDB fibres is due to an influx through L-type Ca2+ channels, and an excess ROS production.
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Pournara, Panagiota [Verfasser]. "Untersuchungen zur Toxikokinetik von Acrylamid und seiner Metabolite N-acetyl-S-(2-carbamoyl-ethyl)-cystein und N-acetyl-S-(2-carbamoyl-2-hydroxy-ethyl)-cystein nach oraler Aufnahme acrylamidhaltiger Nahrung / Panagiota Pournara." Köln : Deutsche Zentralbibliothek für Medizin, 2010. http://d-nb.info/1005360065/34.
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Liu, Chen-Wang, and 劉振旺. "Protective Effects of Garlic Water-soluble Compound N-Acetyl-Cysteine on Leukemia Mice." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/30537179967780275759.
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碩士<br>國立屏東科技大學<br>生物科技系所<br>104<br>N-Acetyl-cysteine (NAC) is an acetylated variant of the amino acid L-cysteine, is an effective antioxidant which can protect cells against oxidative stress. However, the possible protective roles of N-Acetyl-cysteine in WEHI-3-induced leukemia mice has never investigated. The protective activity of NAC on WEHI-3-induced leukemia mice was examined. Twelve BALB/c mice weighing 20g were randomly divided into three groups as follows: the first group was injected PBS and served as the control group; the second group was injected WEHI-3 leukemia cells; the third group was given NAC at a dose of 50mg/kg and then injected WEHI-3 leukemia cells. The experiment lasted a month, WEHI-3 leukemia cells injected only once at the initial. We examined the effects of NAC on the gross examination of organs, weight of mice liver and spleen. The capacity of antioxidants in vivo is determined by assessment of superoxide dismutase (SOD) activity assay and total antioxidant capacity (TAC) colorimetric assay in liver, spleen and serum. We use the Western blot method to recognize NAC inhibition p53 / p38 / caspase-3 path activaty effect in the liver of leukemia mice.Our results indicated NAC revealed the moderate antioxidant activity and protect effect against leukemia in mice.
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Lai, Yung-Chieh, and 雷詠捷. "Synthesis and preparation the N-Acetyl-L-cysteine based nanogel as the drug carrier." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/ny4343.
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碩士<br>國立東華大學<br>生命科學系<br>102<br>N-Acetyl-L-cysteine (NAC), a scavenger for active oxygen,exhibits anti-inflammatory effect .It contains multiple disulfide bonds synthesized to degrade after delivery of drug into the cell.It can also simultaneously act as glutathione (GSH) precursor. New carriers for triggered intracellular were investigated due to in cellular defense anti oxidative damage. 1,6-Diaminohexane was used for the synthesis of organic compounds, because the polymer compound aggregates. The purpose of this study is to design the drug delivery system by using N-Acetyl-L-cysteine（NAC）and apply the devised to control the release of drugs with DTT added to break the disulfide bonds. In this experiment, physicochemical charac-
teristics of N-Acetyl-L-cysteine (NAC) ,1,6-Diaminohexane and DMSO solvent mixture were analyzed by gel electrophoresis, FT-IR,NMR,mass spectrometry(MS) to identify its structure and molecnlar weignt. Particle size and ú-potential measurements were performed. 1-(3-Dimethylamin- opropyl)-3-ethylcarbodiimide (EDC) activator and N-hydroxysulfosuccinimide sodium salt (NHS) auxiliary agents activated COOH group as a reaction. The Estradiol embedded was confirmed by a dialysis technique. Adding DTT to the synthetic polymers, was to investigate the release of the drug in the cytoplasm.
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Hung-Hsuan and 鄭弘萱. "Effect of N-acetyl cysteine on curcumin inhibiting telomerase activity in A549 lung carcinoma cells." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/27938455440244923109.
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碩士<br>中山醫學大學<br>醫學分子毒理學研究所<br>97<br>Telomerase is a special ribonucleoprotein for synthesizing the telomeric DNA at the ends of chromosomes. Telomerase activity is suppressed in normal human somatic tissues, but it is activated in 85~90% tumor tissues. So inhibiting telomerase activity is a useful therapeutic strategy. Curcumin, the yellow pigment in turmeric, is known to inhibit proliferation of cancer cells by arresting them at various phases of the cell cycle and to induce apoptosis in tumor cells. This study mainly explored that curcumin suppress telomerase activity throuh ROS production in A549 cells. First, curcumin inhibited A549 telomerase activity by telomerase repeat amplification protocol. Using Western blot and RT-PCR, curcumin reduced h.TERT expression in a dose dependent manner. The reporter assay show that curcumin suppress the h.TERT promoter expression through Sp1. DNA affinity precipitation assay was used to confirm that curcumin inhibited Sp1 binding on the h.TERT promoter. In addition, we analyzed that curcumin could induce calcium ion production by Flow cytometry in A549 cells. A549 cells were treated with calcium ion inhibitor of BAPTA-AM and Nifedipine, which did not recover the h.TERT supperession by curcumin. Therefore, our data suggested that suppression of telomerase activity is independent on calcium ion production. Furthermore, N-acetyl cysteine (NAC) restored the telomerase activity suppression by curcumin. The mRNA and protein expression of h.TERT decreased by curcumin was reversed by NAC. NAC also restored the expression of Sp1 reduction and h.TERT that were downregulation by curcumin. Our results strongey suggested that curcumin induced ROS production which resulted in inhibiting Sp1 binding activity and h.TERT downregulation.
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Phong, Ying-Chiann, and 馮瑩茜. "Effects of N-acetyl cysteine on Lateral Line Hair Cell of Zebrafish Larvae (Danio Rerio)." Thesis, 2019. http://ndltd.ncl.edu.tw/handle/3v3686.
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碩士<br>國立臺灣師範大學<br>生命科學系<br>107<br>N-acetyl cysteine (NAC), an antioxidant used as a nutritional supplement, was used to protect tilapia from oxidative stress-induced by Microcystin and Cylindrospermopsin in the aquaculture sector. The aim of the present study was to investigate the potential toxicity and lethal dose of NAC before applying it to be an antioxidant in fish. Furthermore, we test for the protective effect of NAC against neomycin-induced ototoxicity. We investigate the embryonic toxicity of NAC on zebrafish larvae by acute or chronic exposure to NAC. Our results showed that NAC caused a lethal effect on zebrafish embryo in a dose-dependent manner. By the development assessments, survival rate, body length, and heart rate significantly decreased after the NAC treatment. By labeling hair cells with FM1-43, the hair cells number decreased in both acute and chronic NAC treatment groups. Oxidative stress of lateral line hair cell increased after acute NAC treatment. Moreover, NAC reduced the density of ionocyte on zebrafish yolk sac. Our findings demonstrate that NAC may cause toxicity to zebrafish in both acute and chronic treatment.
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Huang, Szu-Ping, and 黃思萍. "An exposure biomarker of aristolochic acid-containing herbs: aristolochic acid and N-acetyl-L-cysteine adduct." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/6ewhgk.
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Ying, Chang Wen, and 張文茵. "To Determine the Effects of N-Acetyl Cysteine on the Expression of Thrombomodulin in Breast Cancer." Thesis, 2015. http://ndltd.ncl.edu.tw/handle/58226706533223122427.
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碩士<br>國防醫學院<br>生物化學研究所<br>103<br>Reactive oxygen species (ROS) can cause cellular injury by inducing DNA damages which can lead to tumorgenesis. So far, the evidences show that antioxidants can neutralize ROS thereby reducing cell damages. Many studies have found that ROS can promote Epithelial-mesenchymal transition (EMT) of cancer cells, in which can promote cancer metastasis and invasiveness. In addition, the majority of antioxidants are also found to have the effects of prevention or inhibition of EMT. Lots of proteins are known to participate in the EMT process such as Thrombomomodulin (TM). Recently, the dates indicate that TM is the downstream regulatory gene of Snail, which may have a crucial role on EMT process. And, the other results show that the decline of the TM can increase EMT. Furthermore, N-acetylcysteine (NAC), as an antioxidant, has been considered to enhance the functions of the TM. The purpose of this proposal is to investigate the roles of the TM on the breast cancer cells morphology and metastasis under the NAC treatment. The preliminary results show that NAC can upregulate the mRNA and protein levels of TM and inhibit the breast cancer cell migration. NAC can also downregulate the expression of biomarkers of EMT in breast cancer cells.
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Chen, Jia-Shing, and 陳嘉興. "Inhibitory Effects of N-acetyl-L-cysteine on Cell Proliferation and UV Induction of PCNA in CHO-K1 Cells." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/17276217244298459314.
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碩士<br>國立清華大學<br>生命科學系<br>88<br>N-acetyl-L-cysteine (NAC), a well-known antioxidant is a scavenger of free radicals that can remove excess free radicals from cells and protect cells from damage by oxidants. In cycling CHO-K1 cells, NAC can inhibit the proliferation of cells, delay the procession of cell cycle and change the morphology of cells. When the cells are treated by NAC, the morphology of cells changes from normal spindle to abnormal round gradually. But we can''t find the morphology change on quiescent cells. When the medium containing NAC is removed, cell cycle will go ahead and the change of cell morphology will reverse. Proliferating cell nuclear antigen (PCNA), an auxiliary factor of DNA polymerase δandε, is required for eukaryotic cell DNA synthesis and excision repair. Expression of PCNA is growth regulated but can be induced by variable extracellular stimuli including exposure to UV irradiation. We have found that UV-C irradiation can induce PCNA gene expression in CHO.K1 cells, no matter recovering in serum or in serum-free medium. To exclude the effect of serum stimulation, we have treated quiescent cells with NAC before and after UV-C irradiation under serum free condition. We find that NAC can inhibit UV-C induction of PCNA mRNA and protein. Although NAC is a GSH precursor, the inhibitory effect of UV induction of PCNA seems to GSH independent. The results suggest that NAC involves in anti-proliferation of CHO.K1 cells and regulation of UV-C response of PCNA.
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Chung, Li-Yu, and 鍾麗玉. "Oxidative damage caused by infection with Angiostrongylus cantonensis and the mechanism in the treatment with N-acetyl-L-cysteine." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/94745979984818638233.
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博士<br>高雄醫學大學<br>醫學研究所<br>99<br>This study included three aims. The first aim was to estimate reactive oxygen species (ROS) production, antioxidants activity, and biomarkers level of oxidative damage to lipid, protein and DNA in the cerebrospinal fluid (CSF) of C57BL/6 mice infected with Angiostrongylus cantonensis. The ROS concentration in the CSF of infected mice increased gradually, and the increase in ROS in CSF became statistical significance at day 12-30 post-infection compared to that before infection, and then ROS returned to normal level at day 45 after infection. In parallel with the increase in ROS in the CSF, infected mice showed similar of changes in superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione-s-transferase, and glutathione as that in ROS in the CSF. Those antioxidants in the CSF of infected mice were all significant higher than they were before infection. However, malondialdehyde, protein carbonyl content and 8-hydroxy-2’-deoxyguanosine, biomarkers of oxidative to lipid, protein and DNA, respectively, were also significantly higher in the CSF of infected mice during this period. These results suggest that oxidative stress occur in the cells of central nervous system of mice infected with A. cantonensis. The second aim was to know the source of ROS and the regulation factor in the CSF of infected mice. Eosinophils increased in mice after infection and E-, L-selectin, ICAM-1, and VCAM-1 promoted the adherence of eosinophils to vascular endothelial cells, then they transmigrated into the CSF of infected mice. The measurement of CSF eosinophils and brain tissue homogenates found that ROS were from CSF eosinophils. IL-5 was found that it could maintain CSF eosinophils producing ROS in incubation in vitro. The third aim was to estimate the effect of N-acetyl-L-cysteine in the treatment of infected mice and the mechanism in decrease the level of ROS in the CSF of infected mice. In the incubation of CSF eosinophils from infected mice with IL-5 and N-acetyl-L-cysteine, the extracellular ROS produced by eosinophils were scavenged and the intracellular ROS in eosinophils were inhibited by N-acetyl-L-cysteine. The increase leakage of lactic dehydrogenase of eosinophil in culture medium and lower mitochondrial membrane potential of eosinophil became significant 24 hours after incubation. Further more, significantly decrease of P-ERK, significantly higher activity of caspase-3, and lower cytochrome c levels as well as caspase-9 activity were also found in the same incubation. Thus, the ERK route and cytoplasmic caspase-3 were correlated with the apoptosis of CSF eosinophils incubation with N-acetyl-L- cysteine in IL-5 rich medium. The use of N-acetyl-L-cysteine in the treatment of A. cantonensis infection in hosts are helpful in promotion apoptosis of CSF eosinophils and reduction ROS production in CSF. Indeed, 50% of BALB/c mice survived after treatment with N-acetyl-L-cysteine for 12 days at day 12 after infection.
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Liu, Tzu-An, and 劉子安. "Electrochemical Determination of N-acetyl-L-cysteine at Poly(3,4-ethylenedioxythiophene) and Ionic Liquid Composite Film Modified Screen-Printed Carbon Electrodes." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/9pfdf5.
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碩士<br>國立暨南國際大學<br>應用化學系<br>102<br>In this study, we modified a thin layer of poly-3,4-ethylenedioxythiophene (PEDOT) on a bare screen-printed carbon electrode (SPCE) by electrochemical methods, and then ionic liquid ([BMIM+][Cl-]) was fabricated onto SPCE/PEDOT by spin coating. The obtained SPCE/PEDOT/[BMIM+][Cl-] was employed for the determination of N-Acetyl-L-cystenine (NAC) in pH 7.0 buffer. Cyclic voltammetric studies showed two irreversible oxidation potential of NAC at 0.17 V and 0.49 V. It was suggested that the ionic liquid layer can extract NAC and thus lowered overpotentials. The other ionic liquids with different anions (OTf-, NTf2-, BF4-, Br-, PF6-) were examined for NAC detection, and only Br- and PF6- showed the two oxidation peaks.
Excellent analytical features were achieved by flow injection analysis for determination of NAC under optimized conditions, the linear calibration curve was obtained from 10 μM to 600 μM for NAC and the sensitivity was 0.0024 μA/μM. The detection limit (S/N = 3) was 0.25 μM.
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BELLISARIO, VERONICA. "Long-term effects of prenatal exposure to high-fat diet in an animal model of reduced oxidative stress." Doctoral thesis, 2014. http://hdl.handle.net/2158/949357.
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Obesity is a world-wide health problem. The increasing incidence of this pathology among women of reproductive age and children highlights the main question of the role played by maternal obesity in setting up a state of individual susceptibility to metabolic disorders in the adult offspring. A growing body of evidence suggests that maternal obesity and maternal adiposity, per se, are associated with adverse acute maternal and neonatal outcomes. It has been stated that maternal obesity and, more in general, maternal over-nutrition, such as maternal feeding a diet rich in fats (high-fat diet - HFD), are strongly associated with a raised offspring susceptibility to cardiovascular disease (CVD) and metabolic impairment, such as hyperglycaemia and hyperinsulinemia, type 2 diabetes (T2D) and obesity at adulthood. Obesity is a pathophysiological condition characterized by a low-grade chronic inflammation which contributes to the mechanism for obesity-related metabolic syndrome, insulin resistance (IR) and diabetes. Increased physiological levels of oxidative stress (OS) may be causatively linked to the development and progression of complications associated to obesity and over-nutritional state.
Clinical as well as experimental studies support the theory of the “developmental origins of health and disease” according to which the prenatal environmental adversities may exert lifelong consequences by programming the offspring’s development. However, a comprehensive and multi-levels characterization of the long-term impact of maternal HFD is still lacking. In addition, very few studies have paid attention to the long-term effects of exposure to a maternal HFD during the in utero life only. The general aim of the work presented in this thesis was to evaluate the impact of maternal HFD both on mother and offspring in a long-term perspective and to study the effects of metabolic disturbances occurring in a sensitive time window of the individual life (i.e. fetal development and pregnancy) on the stress response, as well as on the metabolic and emotional profiles. We also aimed at investigating the interaction between an early metabolic stimulus (maternal HFD) and a physiological condition of reduced OS.
In particular, in Chapter 2, we report about the long-term effects of prenatal exposure to maternal HFD assessing the metabolic, neuroendocrine as well as the behavioral profile of young adult offspring in a transgenic mouse model characterized by reduced oxidative stress, the p66Shc-/-.
In Chapter 3 we report the effects of a prenatal exposure to N-acetyl-cysteine, a drug characterized by remarkable antioxidant properties, to thwart the physiological response to maternal HFD in utero. These studies relied on the assessment of a physiological (Chapter 2) or pharmacological (Chapter 3) condition of reduced OS able to represent a protective condition toward the maternal HFD.
Chapter 4 describes the effects of HFD feeding before and during pregnancy on the neuroendocrine and behavioral profile of dams in the perinatal period. In addition, in this chapter we propose to investigate the potential role of HFD as a metabolic stressor for the mother with a negative impact for the developing fetus.
Results are discussed considering the impact of HFD feeding during pregnancy on the dam and the possible consequences on the offspring at multiple levels (behavioral, metabolic and endocrine). Particular attention has been paid to a physiological or pharmacological condition of reduced OS as a potential protective factor. Results obtained in this thesis might drive the attention on selected markers useful to detect potential unhealthy states and to develop future preventive strategies as well as pharmacological therapies to limit the effects associated to maternal HFD.
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Li, Cheng-Feng, and 李承峰. "Regulation of the PI3K/AKT Signaling Pathway by Advanced Glycation End-products, High Glucose and N-acetyl-L-cysteine in 3T3-L1 Preadipocytes." Thesis, 2012. http://ndltd.ncl.edu.tw/handle/93017652716385956940.
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Kashyap, Srishti. "Isolation, Structure Elucidation and Functional Characterization of a Novel Cytotoxic Secondary Metabolite Phomafuranone, 2-Hydroxy-2, 4-dimethyl-5-[-1-propen-1-yl]-3(2H)-furanone, from Phoma tropica an Endophytic Fungus Isolated from Mappia foetida." Thesis, 2017. http://etd.iisc.ac.in/handle/2005/4135.
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Cancer has become the leading disease-related cause of death in the human population. For example, in the United States, cancer is the second leading cause of death behind cardiovascular disease, and it is projected that cancer will become the leading cause of death in the coming years. The medical treatment of cancer still has many unmet needs. The main curative therapies for cancer, surgery and radiation, are generally only successful if the cancer is found at an early localized stage. Once cancer has progressed to metastatic stage, these therapies are less successful. Hence, chemotherapeutic drugs are used for the treatment of these advanced tumors, particularly in the case of the common epithelial tumors such as lung, colorectal, breast, prostate, and pancreatic cancers. New chemotherapeutic drugs are necessary since most of the cancers acquire resistance towards existing anticancer drugs.
Nature has always been an attractive source of new chemotherapeutic agents, as a tremendous chemical diversity is found in millions of species of plants, animals, and microorganisms.Microorganisms (bacteria, fungi, actinomycetes) serve as readily renewable and inexhaustible source of novel bioactive metabolites.Endophyte, a microorganism that reside in theinternal tissues of living plantswithout causing any immediate overt negative effects, are potential sources of novel natural products for exploitation in medicine.
Mappia foetidais distributed in western part of peninsular coastal India from Konkanghatsto northern parts of the Kanara, Nilgiris, Anamalis, and Pullneys hills of India. It is a rich source of alkaloids such as camptothecin, 9-methoxy camptothecin, mappicin,sitosterol and lupeol and other natural products having anticancer and antimicrobial properties. Since, the secondary metabolite production in fungal endophytes is greatly influenced by theircompetitive ecological niche and interaction with host metabolism, Mappia foetida was chosen for endophytic fungal isolation. Sirsi, (North Karnataka, India) because of its rich biodiversity was chosen as a location for collection of the plant samples.
The organicsolvent extracts obtained from mycelia and culture filtrates of all the endophytic fungal isolates were screened for their cytotoxic activity against HeLa (human cervical carcinoma) cellline. Organic extracts of 8 fungal isolates exhibited significant cytotoxic activity, among which Phoma tropica(S1/3) culture filtrate extract exhibited most significant cytotoxicactivity againstHeLa cell line with IC50 of 25µg/ml.
Dichloromethane extract of the Phoma tropica culture filtrate was subjected to bioassay–guided column chromatographic fractionationwhich resulted in the isolation of purified cytotoxic secondary metabolite. Based on the analysis of variousspectroscopic techniques such as NMR, FTIR, LC-MS/MS, HRMS, CHNOS elemental analysis and X-ray diffraction studies, the purified metabolite was identified as 2-Hydroxy-2,4-dimethyl-5-[-1-propen-1-yl]-3(2H)furanone(Phomafuranone).Phomafuranone exhibited significant cytotoxic activity against various cancer cell lines (HeLa, Jurkat, COLO 205, HT-29, HCT-15, HCT 116, A549, A-431 and OVCAR-3)
Further studies were undertaken to elucidate the mechanism of cytotoxicityof the purified metabolite on human cancer cell lines. Phomafuranone contains a conjugated unsaturated α, β, γ, δ carbonyl pharmacophore moiety. Polyunsaturated carbonyl compounds are referred to as “Michael acceptors” and they behave as soft electrophiles. Michael acceptors react with strong biological nucleophiles such as thiols.The reactivity of electrophilic Phomafuranone with thiol containing biomolecules like glutathione, cysteine and N-acetyl cysteine was investigated by spectrophotometric methods.
Cell cycle progressionanalyses oftreated HCT 116 (colorectal carcinoma) cell line by flow cytometry revealed that Phomafuranone arrested significant proportion of cells in G2/M phase. HCT 116 cells were arrested specifically in early mitotic phase of cell cycle as indicated by time dependent increase in phospo-histone3 (Ser10) levels and nuclear import of Cyclin B1.On treatment cancer cells with Phomafuranone, time dependent depletion of intracellular reduced glutathione levels was observed. Depletion of reduced glutathione inturn led to elevated intracellular ROS levels.Pre-treatment of HCT 116 cell lines with thiol containing antioxidants like N- acetylcysteine (NAC) and reduced glutathione (GSH) completely abrogated itscytotoxic effect, suggesting Phomafuranone inducedthiol–mediated cytotoxicity. The elevated ROS levels led to mitochondrial membrane depolarization as indicated by cytochrome c release in cytosol from mitochondria in a time dependent manner. Cytochrome c release was followed caspase 9 mediated apoptotic cell death. Thus, our results suggest that Phomafuranone induced redox imbalancemediated apoptosis in HCT 116 cell line by intrinsic pathway.
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Kraus, Torsten. "Entgiftung lipophiler Xenobiotika - die Cystein-S-Konjugat-spezifische N-Acetyl-S-Transferase." Phd thesis, 2000. http://tuprints.ulb.tu-darmstadt.de/58/1/Kraus_Tor.pdf.
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Lebewesen, wie auch der Mensch, sind in der Natur einer Vielzahl von schädlichen Substanzen ausgesetzt. Zum einen sind Schadsubstanzen natürlichen Ursprungs, zum anderen gelangen sie aufgrund anthropogener Wirkungen in die Biosphäre. Gegenüber organischen niedermolekularen Substanzen, die nicht für das Überleben des Organismus notwendig sind, wurden im Laufe der Evolution Mechanismen entwickelt, eine in den Körper aufgenommene Verbindung auszuschleusen. Häufig handelt es sich dabei um potentiell schädliche Chemikalien. Die Entgiftung lipophiler Fremdsubstanzen (Xenobiotika) kann in drei Phasen unterteilt werden. In der ersten Phase findet eine Funktionalisierung des Substrates statt. Dabei wird eine funktionelle Gruppe enzymatisch auf das Substrat übertragen. In der zweiten Phase wird das funktionalisierte Substrat mit einer endogenen Verbindung, wie z.B. Glutathion, konjugiert. Dadurch wird die Polarität und somit die Hydrophilie des Xenobiotikums erhöht. Dies vermindert das toxische Potential und ermöglicht die Ausscheidung (Phase III). Ein wichtiger Weg, über den lipophile Xenobiotika ausgeschleust werden können, ist der Mercaptursäureweg der Entgiftung. Im ersten Schritt erfolgt die Konjugation mit dem Tripeptid Glutathion. Das Glutathion-Konjugat wird in der Folge schrittweise enzymatisch zu einem Cystein-S -Konjugat hydrolysiert. Das Cystein-S -Konjugat ist das Substrat für die membrangebundene N ?Acetyl-S -Transferase (NAcT, EC 2.3.1.80), die Gegenstand der Untersuchungen dieser Arbeit ist. Das Cystein-S -Konjugat wird meist in der Niere acetyliert und über den Urin ausgeschieden. Es entsteht ein N ?Acetyl?Cystein?S ?Konjugat, das auch als Mercaptursäure bezeichnet wird. Viele technisch wichtige Substanzen gehören der Stoffklasse der Haloalkane oder Haloalkene an, die über den Mercaptursäureweg entgiftet werden. Dabei können aufgrund von Konkurrenzreaktionen (z. B. katalysiert durch b-Lyase) toxische und cancerogene Metabolite entstehen. Die Toxizität einer Verbindung ist somit ein Maß für das Gleichgewicht, das zwischen der Acetylierung und den Konkurrenzreaktionen besteht. Für Haloalkane bzw. Haloalkene ist deshalb die Kenntnis der kinetischen Konstanten Km und Vmax dieser Reaktionen von Bedeutung. Im Rahmen der Arbeit wurden die kinetischen Konstanten der N ?Acetylierung für verschiedene Haloalkyl- und Haloalkenyl-Cystein-S ?Konjugaten (von Dr. M. W. Anders, Rochester, NY zur Verfügung gestellt) bestimmt. Dazu wurde ein quantitativ auswertbarer, radioaktiver Aktiviätstest etabliert. Das Teilreinigungverfahren für die NAcT aus der Niere wurde optimiert und konkurrierende Enzymaktivitäten (Deacetylase, Acetyl-CoA Hydrolase) konnten vollständig, bzw. fast vollständig abgetrennt werden. Aus einer früheren Arbeit [Aigner, 1995] lagen Phagenklone vor, die bei Durchmusterung einer cDNA-Expressionsbank mit einem gegen NAcT-spezifischen Antikörper erhalten worden waren. Die DNA-Sequenzen dieser Klone wurden im Rahmen der vorliegenden Arbeit ermittelt. Gemeinsame Merkmale aller cDNA-Insertionen ist die Übereinstimmung mit Proteinen, die über eine ATP-Bindestelle verfügen und an DNA binden.
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Kraus, Torsten [Verfasser]. "Entgiftung lipophiler Xenobiotika - die Cystein-S-Konjugat-spezifische N-Acetyl-S-Transferase : ein repräsentatives Enzym des Mercaptursäureweges / von Torsten Kraus." 1999. http://d-nb.info/960529950/34.
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Shee, Somnath. "Manipulating Bacterial and Host Reactive Oxygen Species (ROS)- based mechanisms to potentiate killing of Mycobacterium tuberculosis (Mtb)." Thesis, 2021. https://etd.iisc.ac.in/handle/2005/5680.
Full textAbstract:
Mycobacterium tuberculosis (Mtb) is evolutionarily equipped to resist exogenous reactive oxygen species but shows vulnerability to an increase in endogenous ROS (eROS). Since eROS is an unavoidable consequence of aerobic metabolism, understanding how eROS levels are controlled is essential yet remains uncharacterized. By combining the Mrx1-roGFP2 redox biosensor with transposon mutagenesis, we identified 368 genes (redoxosome) responsible for maintaining non-toxic levels of eROS in Mtb. Integrating redoxosome with a global network of protein-protein interactions and transcriptional regulators revealed a hypothetical protein (rv0158) as a top node managing eROS and redox homeostasis in Mtb. RNA sequencing, seahorse XF flux measurements, and lipid analysis indicate that rv0158 is required to balance the deployment of fatty acid substrates between lipid anabolism and oxidation. Disruption of rv0158 perturbed redox balance in a carbon-source-specific manner, promoted killing in response to anti-TB drugs, reduced survival in macrophages, and lowered persistence in mice.
We describe a novel pathogen response to moxifloxacin. Mtb, unlike Escherichia coli, decreases respiration in response to moxifloxacin. Nevertheless, cells were killed, as ROS increased due to NADH-dependent reductive stress. Moxifloxacin lethality was mitigated by supplementing bacterial cultures with a ROS scavenger (thiourea), and an iron chelator (bipyridyl), indicating ROS is part and not a consequence of death processes. Treatment with N-acetyl cysteine (NAC) accelerated respiration and ROS production, increased moxifloxacin lethality, and lowered the mutant prevention concentration. Thus, redox and bioenergetic imbalance contribute to the moxifloxacin-mediated killing of Mtb. These results provide a way to make fluoroquinolones more effective anti-tuberculosis agents.
We have previously reported that Mtb H37Rv sets up a gradient of mycothiol redox potential: EMSH-oxidized (-240 mV) to EMSH-reduced (-320 mV) inside macrophages, where the EMSH -reduced Mtb subpopulation are significantly more tolerant to anti-TB drugs. Therefore, one of the keys to subverting drug-tolerance is to impede the emergence of EMSH -reduced subpopulation by inducing overwhelming oxidative stress. In this study, we exposed THP1-macrophages infected with Mtb H37Rv expressing Mrx1-roGFP2-biosensor, to a library of FDA-approved drugs (Enzo Life Sciences; BML-2842) and scored for the oxidative shift in the Mtb- EMSH at 24 hours post infection. Based on their activity to trigger oxidative stress inside the bacterium, non-cytotoxicity to host, and inhibition of bacterial growth inside macrophages, C5 molecule emerged as the top hit. Pre-treatment with C5 potentiated killing of Mtb by all tested antibiotics (isoniazid, rifampicin, and moxifloxacin) and reduced drug-tolerance.<br>Welcome-DBT