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1
Karwowska, Małgorzata, and Anna Kononiuk. "Nitrates/Nitrites in Food—Risk for Nitrosative Stress and Benefits." Antioxidants 9, no. 3 (March 16, 2020): 241. http://dx.doi.org/10.3390/antiox9030241.
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In the context of impact on human health, nitrite/nitrate and related nitrogen species such as nitric oxide (NO) are a matter of increasing scientific controversy. An increase in the content of reactive nitrogen species may result in nitrosative stress—a deleterious process, which can be an important mediator of damage to cell structures, including lipids, membranes, proteins and DNA. Nitrates and nitrites are widespread in the environment and occur naturally in foods of plant origin as a part of the nitrogen cycle. Additionally, these compounds are used as additives to improve food quality and protect against microbial contamination and chemical changes. Some vegetables such as raw spinach, beets, celery and lettuce are considered to contain high concentrations of nitrates. Due to the high consumption of vegetables, they have been identified as the primary source of nitrates in the human diet. Processed meats are another source of nitrites in our diet because the meat industry uses nitrates/nitrites as additives in the meat curing process. Although the vast majority of consumed nitrates and nitrites come from natural vegetables and fruits rather than food additives, there is currently a great deal of consumer pressure for the production of meat products free of or with reduced quantities of these compounds. This is because, for years, the cancer risks of nitrates/nitrites have been considered, since they potentially convert into the nitrosamines that have carcinogenic effects. This has resulted in the development and rapid expansion of meat products processed with plant-derived nitrates as nitrite alternatives in meat products. On the other hand, recently, these two ions have been discussed as essential nutrients which allow nitric oxide production and thus help cardiovascular health. Thus, this manuscript reviews the main sources of dietary exposure to nitrates and nitrites, metabolism of nitrites/nitrates, and health concerns related to dietary nitrites/nitrates, with particular emphasis on the effect on nitrosative stress, the role of nitrites/nitrates in meat products and alternatives to these additives used in meat products.
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Rajeev, Lara, Amy Chen, Alexey E. Kazakov, Eric G. Luning, Grant M. Zane, Pavel S. Novichkov, Judy D. Wall, and Aindrila Mukhopadhyay. "Regulation of Nitrite Stress Response in Desulfovibrio vulgaris Hildenborough, a Model Sulfate-Reducing Bacterium." Journal of Bacteriology 197, no. 21 (August 17, 2015): 3400–3408. http://dx.doi.org/10.1128/jb.00319-15.
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ABSTRACTSulfate-reducing bacteria (SRB) are sensitive to low concentrations of nitrite, and nitrite has been used to control SRB-related biofouling in oil fields.Desulfovibrio vulgarisHildenborough, a model SRB, carries a cytochromec-type nitrite reductase (nrfHA) that confers resistance to low concentrations of nitrite. The regulation of this nitrite reductase has not been directly examined to date. In this study, we show that DVU0621 (NrfR), a sigma54-dependent two-component system response regulator, is the positive regulator for this operon. NrfR activates the expression of thenrfHAoperon in response to nitrite stress. We also show thatnrfRis needed for fitness at low cell densities in the presence of nitrite because inactivation ofnrfRaffects the rate of nitrite reduction. We also predict and validate the binding sites for NrfR upstream of thenrfHAoperon using purified NrfR in gel shift assays. We discuss possible roles for NrfR in regulating nitrate reductase genes in nitrate-utilizingDesulfovibriospp.IMPORTANCEThe NrfA nitrite reductase is prevalent across several bacterial phyla and required for dissimilatory nitrite reduction. However, regulation of thenrfAgene has been studied in only a few nitrate-utilizing bacteria. Here, we show that inD. vulgaris, a bacterium that does not respire nitrate, the expression ofnrfHAis induced by NrfR upon nitrite stress. This is the first report of regulation ofnrfAby a sigma54-dependent two-component system. Our study increases our knowledge of nitrite stress responses and possibly of the regulation of nitrate reduction in SRB.
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Stojanović, Nikola M., Pavle J. Randjelović, Dragana Pavlović, Nenad I. Stojiljković, Ivan Jovanović, Dušan Sokolović, and Niko S. Radulović. "An Impact of Psychological Stress on the Interplay between Salivary Oxidative Stress and the Classic Psychological Stress-Related Parameters." Oxidative Medicine and Cellular Longevity 2021 (January 7, 2021): 1–8. http://dx.doi.org/10.1155/2021/6635310.
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Both oxidative and psychological (mental) stress are the likely culprits for several acute and chronic health disturbances, and adequate tests mimicking that are needed. Herein, in controlled laboratory surroundings, a PEBL (Psychology Experiment Building Language) test battery was used to evoke stress-related biological responses followed by tracking changes in saliva parameters. The study objectives were to determine the impact of psychological stress on selected salivatory parameters and to assess the correlation between the determined oxidative and stress parameters. The study was conducted on 36 healthy young subjects, mainly females ( n = 24 ). Before and following the completion of a battery of four PEBL tests, subjects’ saliva samples were collected. Stress-evoking changes in total antioxidant capacity and nitrite/nitrate levels, as oxidative stress parameters, and cortisol and immunoglobulin A (IgA), as parameters of psychological stress, were established and mutually correlated by comparing the values of the evaluated parameters pre- and post-PEBL test. The results showed that there is no change in the total salivary antioxidant capacity ( p > 0.05 ); however, there was a significant increase in nitrites/nitrates levels after the PEBL test ( p = 0.007 ). On the other hand, the determined cortisol levels after the test battery were found to be statistically significantly increased ( p = 0.025 ) when compared to the values obtained before the test, while the levels of IgA were found to be statistically significantly decreased ( p < 0.001 ). The only statistically significant correlation between the changes in the studied parameters was found to be the one between cortisol and IgA levels (Spearman’s Rö = -0.4). These results suggest that the short-term stress induced by the PEBL test does evoke changes in the salivary mental stress-related parameters (an increase in cortisol and nitrite/nitrate levels, and a decrease in IgA), but not in the total antioxidant capacity. They also indicate that the constructed PEBL four-test battery might represent an adequate laboratory stress-inducing paradigm.
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Stojanović, Nikola M., Pavle J. Randjelović, Dragana Pavlović, Nenad I. Stojiljković, Ivan Jovanović, Dušan Sokolović, and Niko S. Radulović. "An Impact of Psychological Stress on the Interplay between Salivary Oxidative Stress and the Classic Psychological Stress-Related Parameters." Oxidative Medicine and Cellular Longevity 2021 (January 7, 2021): 1–8. http://dx.doi.org/10.1155/2021/6635310.
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Both oxidative and psychological (mental) stress are the likely culprits for several acute and chronic health disturbances, and adequate tests mimicking that are needed. Herein, in controlled laboratory surroundings, a PEBL (Psychology Experiment Building Language) test battery was used to evoke stress-related biological responses followed by tracking changes in saliva parameters. The study objectives were to determine the impact of psychological stress on selected salivatory parameters and to assess the correlation between the determined oxidative and stress parameters. The study was conducted on 36 healthy young subjects, mainly females ( n = 24 ). Before and following the completion of a battery of four PEBL tests, subjects’ saliva samples were collected. Stress-evoking changes in total antioxidant capacity and nitrite/nitrate levels, as oxidative stress parameters, and cortisol and immunoglobulin A (IgA), as parameters of psychological stress, were established and mutually correlated by comparing the values of the evaluated parameters pre- and post-PEBL test. The results showed that there is no change in the total salivary antioxidant capacity ( p > 0.05 ); however, there was a significant increase in nitrites/nitrates levels after the PEBL test ( p = 0.007 ). On the other hand, the determined cortisol levels after the test battery were found to be statistically significantly increased ( p = 0.025 ) when compared to the values obtained before the test, while the levels of IgA were found to be statistically significantly decreased ( p < 0.001 ). The only statistically significant correlation between the changes in the studied parameters was found to be the one between cortisol and IgA levels (Spearman’s Rö = -0.4). These results suggest that the short-term stress induced by the PEBL test does evoke changes in the salivary mental stress-related parameters (an increase in cortisol and nitrite/nitrate levels, and a decrease in IgA), but not in the total antioxidant capacity. They also indicate that the constructed PEBL four-test battery might represent an adequate laboratory stress-inducing paradigm.
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De Luca, Chiara, Agnese Gugliandolo, Carlo Calabrò, Monica Currò, Riccardo Ientile, Desanka Raskovic, Ludmila Korkina, and Daniela Caccamo. "Role of Polymorphisms of Inducible Nitric Oxide Synthase and Endothelial Nitric Oxide Synthase in Idiopathic Environmental Intolerances." Mediators of Inflammation 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/245308.
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Oxidative stress and inflammation play a pathogenetic role in idiopathic environmental intolerances (IEI), namely, multiple chemical sensitivity (MCS), fibromyalgia (FM), and chronic fatigue syndrome (CFS). Given the reported association of nitric oxide synthase (NOS) gene polymorphisms with inflammatory disorders, we aimed to investigate the distribution of NOS2A −2.5 kb (CCTTT)nas well as Ser608Leu and NOS3 −786T>C variants and their correlation with nitrite/nitrate levels, in a study cohort including 170 MCS, 108 suspected MCS (SMCS), 89 FM/CFS, and 196 healthy subjects. Patients and controls had similar distributions of NOS2A Ser608Leu and NOS3 −786T>C polymorphisms. Interestingly, the NOS3 −786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients. We also found that the NOS2A −2.5 kb (CCTTT)11allele represents a genetic determinant for FM/CFS, and the (CCTTT)16allele discriminates MCS from SMCS patients. Instead, the (CCTTT)8allele reduces by three-, six-, and tenfold, respectively, the risk for MCS, SMCS, and FM/CFS. Moreover, a short number of (CCTTT) repeats is associated with higher concentrations of nitrites/nitrates. Here, we first demonstrate that NOS3 −786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A −2.5 kb (CCTTT)npolymorphism may be useful for differential diagnosis of various IEI.
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Förster, Moritz, Christopher Nelke, Saskia Räuber, Hans Lassmann, Tobias Ruck, Maria Pia Sormani, Alessio Signori, et al. "Nitrosative Stress Molecules in Multiple Sclerosis: A Meta-Analysis." Biomedicines 9, no. 12 (December 14, 2021): 1899. http://dx.doi.org/10.3390/biomedicines9121899.
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Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system of unknown etiology. As it is still a diagnosis of exclusion, there is an urgent need for biomarkers supporting its diagnosis. Increasing evidence suggests that nitrosative stress may play a pivotal role in the pathogenesis of MS. However, previous reports supporting the role of nitrosative stress molecules as disease biomarkers are inconsistent overall. We therefore systematically analyzed the existing literature to compare the serum and cerebrospinal fluid (CSF) levels of nitrite/nitrate in MS patients with those in patients with noninflammatory other neurological diseases (NIOND) and healthy controls (HC), respectively. We searched the PubMed database and included original articles investigating nitrite/nitrate levels in MS patients and NIOND patients or HC based on predefined selection criteria. Effect sizes were estimated by the standardized mean difference using a random effects model. Our results suggest that MS is associated with higher nitrite/nitrate levels within the CSF compared with patients with NIOND (SMD of 1.51; 95% CI: 0.72, 2.30; p = 0.0008). Likewise, nitrite/nitrate in the CSF of MS patients trends towards increased levels compared with those of HC but does not reach statistical significance (SMD of 3.35; 95% CI: −0.48, 7.19; p = 0.07). Measurement of nitrite/nitrate in the CSF might be a valuable tool facilitating the differentiation of MS and NIOND. Further studies with more homogeneous study criteria are needed to corroborate this hypothesis.
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Gruber, H.-J., C. Bernecker, A. Lechner, S. Weiss, M. Wallner-Blazek, A. Meinitzer, G. Höbarth, et al. "Increased nitric oxide stress is associated with migraine." Cephalalgia 30, no. 4 (September 1, 2009): 486–92. http://dx.doi.org/10.1111/j.1468-2982.2009.01964.x.
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Nitric oxide (NO) has been implicated in migraine attacks, but the role of NO in migraine remains unclear. We here hypothesize that increased NO in the headache-free period is associated with migraine. One hundred and thirty probands participated in this study. Various parameters of the NO pathway, such as nitrate, nitrite, arginine, citrulline, nitrosylated proteins, asymmetric dimethylarginine, symmetrical dimethylarginine, expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase and two polymorphisms of eNOS were investigated. We found significant increased nitrate and decreased nitrite levels in migraineurs in the headache-free period. Nitrate and nitrite levels showed a significant inverse correlation. Logistic regression revealed an odds ratio of 3.6 for migraine. Other parameters of the NO pathway were neither altered in migraineurs nor correlated with nitrate. We show here that migraine patients suffer under sustained increased nitrosative stress in the headache-free period, which is associated with a 3.6-fold higher risk for migraine.
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Kern, Melanie, Christine Winkler, and Jörg Simon. "Respiratory nitrogen metabolism and nitrosative stress defence in ϵ-proteobacteria: the role of NssR-type transcription regulators." Biochemical Society Transactions 39, no. 1 (January 19, 2011): 299–302. http://dx.doi.org/10.1042/bst0390299.
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ϵ-Proteobacteria form a globally ubiquitous group of ecologically significant organisms and comprise a diverse range of host-associated and free-living species. To grow by anaerobic respiration, many ϵ-proteobacteria reduce nitrate to nitrite followed by either nitrite ammonification or denitrification. Using the ammonifying model organisms Wolinella succinogenes and Campylobacter jejuni, the electron transport chains of nitrate respiration, respiratory nitrite ammonification and even N2O (nitrous oxide) respiration have been characterized in recent years, but knowledge on nitrosative stress defence, nitrogen compound-sensing and corresponding signal transduction pathways is limited. The potentially dominant role of NssR (nitrosative stress-sensing regulator)-type transcription regulators in ϵ-proteobacterial nitrogen metabolism is discussed.
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Sun, Dong, An Huang, Ellen H. Yan, Zhiping Wu, Changdong Yan, Pawel M. Kaminski, Tim D. Oury, Michael S. Wolin, and Gabor Kaley. "Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats." American Journal of Physiology-Heart and Circulatory Physiology 286, no. 6 (June 2004): H2249—H2256. http://dx.doi.org/10.1152/ajpheart.00854.2003.
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We hypothesized that aging is characterized by a reduced release of nitric oxide (NO) in response to shear stress in resistance vessels. Mesenteric arterioles and arteries of young (6 mo) and aged (24 mo) male Fischer 344 rats were isolated and cannulated. Shear stress (15 dyn/cm2)-induced dilation was significantly reduced and shear stress (1, 5, 10, and 15 dyn/cm2)-induced increases in perfusate nitrite were significantly smaller at all shear stress levels in vessels of aged rats. Inhibition of NO synthesis abolished shear stress-induced release of nitrite. Furthermore, shear stress (15 dyn/cm2)-induced release of nitrate was significantly higher and total nitrite (nitrite plus nitrate) was significantly lower in vessels of aged rats. Tiron or SOD significantly increased nitrite released from vessels of aged rats, but this was still significantly less than that in young rats. Superoxide production was increased and the activity of SOD was decreased in vessels of aged rats. There were no differences in endothelial NO synthase (eNOS) protein and basal activity or in Cu/Zn-SOD and Mn-SOD proteins in vessels of the two groups, but extracellular SOD was significantly reduced in vessels of aged rats. Maximal release of NO induced by shear stress plus ACh (10−5 M) was comparable in the two groups, but phospho-eNOS in response to shear stress (15 dyn/cm2) was significantly reduced in vessels of aged rats. These data suggest that an increased production of superoxide, a reduced activity of SOD, and an impaired shear stress-induced activation of eNOS are the causes of the decreased shear stress-induced release of NO in vessels of aged rats.
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Liu, Jianfeng, Jiao Yin, Yanshuang Li, Dingjin Li, Jiaxuan Wu, Chengxian Wang, Changmei Wang, Fang Yin, Bin Yang, and Wudi Zhang. "High nitrite–nitrogen stress intensity drives nitrite anaerobic oxidation to nitrate and inhibits methanogenesis." Science of The Total Environment 832 (August 2022): 155109. http://dx.doi.org/10.1016/j.scitotenv.2022.155109.
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Cordero-Herrera, Isabel, Mikael Kozyra, Zhengbing Zhuge, Sarah McCann Haworth, Chiara Moretti, Maria Peleli, Mayara Caldeira-Dias, et al. "AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis." Proceedings of the National Academy of Sciences 116, no. 1 (December 17, 2018): 217–26. http://dx.doi.org/10.1073/pnas.1809406115.
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Advanced age and unhealthy dietary habits contribute to the increasing incidence of obesity and type 2 diabetes. These metabolic disorders, which are often accompanied by oxidative stress and compromised nitric oxide (NO) signaling, increase the risk of adverse cardiovascular complications and development of fatty liver disease. Here, we investigated the therapeutic effects of dietary nitrate, which is found in high levels in green leafy vegetables, on liver steatosis associated with metabolic syndrome. Dietary nitrate fuels a nitrate–nitrite–NO signaling pathway, which prevented many features of metabolic syndrome and liver steatosis that developed in mice fed a high-fat diet, with or without combination with an inhibitor of NOS (l-NAME). These favorable effects of nitrate were absent in germ-free mice, demonstrating the central importance of host microbiota in bioactivation of nitrate. In a human liver cell line (HepG2) and in a validated hepatic 3D model with primary human hepatocyte spheroids, nitrite treatment reduced the degree of metabolically induced steatosis (i.e., high glucose, insulin, and free fatty acids), as well as drug-induced steatosis (i.e., amiodarone). Mechanistically, the salutary metabolic effects of nitrate and nitrite can be ascribed to nitrite-derived formation of NO species and activation of soluble guanylyl cyclase, where xanthine oxidoreductase is proposed to mediate the reduction of nitrite. Boosting this nitrate–nitrite–NO pathway results in attenuation of NADPH oxidase-derived oxidative stress and stimulation of AMP-activated protein kinase and downstream signaling pathways regulating lipogenesis, fatty acid oxidation, and glucose homeostasis. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against liver steatosis associated with metabolic dysfunction.
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Raat, Nicolaas J. H., Audrey C. Noguchi, Virginia B. Liu, Nalini Raghavachari, Delong Liu, Xiuli Xu, Sruti Shiva, Peter J. Munson, and Mark T. Gladwin. "Dietary nitrate and nitrite modulate blood and organ nitrite and the cellular ischemic stress response." Free Radical Biology and Medicine 47, no. 5 (September 1, 2009): 510–17. http://dx.doi.org/10.1016/j.freeradbiomed.2009.05.015.
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Nebl, Josefine, Kathrin Drabert, Sven Haufe, Paulina Wasserfurth, Julian Eigendorf, Uwe Tegtbur, Andreas Hahn, and Dimitrios Tsikas. "Exercise-Induced Oxidative Stress, Nitric Oxide and Plasma Amino Acid Profile in Recreational Runners with Vegetarian and Non-Vegetarian Dietary Patterns." Nutrients 11, no. 8 (August 13, 2019): 1875. http://dx.doi.org/10.3390/nu11081875.
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This study investigated the exercise-induced changes in oxidative stress, nitric oxide (NO) metabolism and amino acid profile in plasma of omnivorous (OMN, n = 25), lacto-ovo-vegetarian (LOV, n = 25) and vegan (VEG, n = 23) recreational runners. Oxidative stress was measured as malondialdehyde (MDA), NO as nitrite and nitrate, and various amino acids, including homoarginine and guanidinoacetate, the precursor of creatine. All analytes were measured by validated stable-isotope dilution gas chromatographic-mass spectrometric methods. Pre-exercise, VEG had the highest MDA and nitrate concentrations, whereas nitrite concentration was highest in LOV. Amino acid profiles differed between the groups, with guanidinoacetate being highest in OMN. Upon acute exercise, MDA increased in the LOV and VEG group, whereas nitrate, nitrite and creatinine did not change. Amino acid profiles changed post-exercise in all groups, with the greatest changes being observed for alanine (+28% in OMN, +21% in LOV and +28% in VEG). Pre-exercise, OMN, LOV and VEG recreational runners differ with respect to oxidative stress, NO metabolism and amino acid profiles, in part due to their different dietary pattern. Exercise elicited different changes in oxidative stress with no changes in NO metabolism and closely comparable elevations in alanine. Guanidinoacetate seems to be differently utilized in OMN, LOV and VEG, pre- and post-exercise.
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Schlag, Steffen, Christiane Nerz, Timo A. Birkenstock, Florian Altenberend, and Friedrich Götz. "Inhibition of Staphylococcal Biofilm Formation by Nitrite." Journal of Bacteriology 189, no. 21 (August 24, 2007): 7911–19. http://dx.doi.org/10.1128/jb.00598-07.
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ABSTRACT Several environmental stresses have been demonstrated to increase polysaccharide intercellular adhesin (PIA) synthesis and biofilm formation by the human pathogens Staphylococcus aureus and Staphylococcus epidermidis. In this study we characterized an adaptive response of S. aureus SA113 to nitrite-induced stress and show that it involves concomitant impairment of PIA synthesis and biofilm formation. Transcriptional analysis provided evidence that nitrite, either as the endogenous product of respiratory nitrate reduction or after external addition, causes repression of the icaADBC gene cluster, mediated likely by IcaR. Comparative microarray analysis revealed a global change in gene expression during growth in the presence of 5 mM sodium nitrite and indicated a response to oxidative and nitrosative stress. Many nitrite-induced genes are involved in DNA repair, detoxification of reactive oxygen and nitrogen species, and iron homeostasis. Moreover, preformed biofilms could be eradicated by the addition of nitrite, likely the result of the formation of toxic acidified nitrite derivatives. Nitrite-mediated inhibition of S. aureus biofilm formation was abrogated by the addition of nitric oxide (NO) scavengers, suggesting that NO is directly or indirectly involved. Nitrite also repressed biofilm formation of S. epidermidis RP62A.
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Sindler, Amy L., Allison E. DeVan, Bradley S. Fleenor, and Douglas R. Seals. "Inorganic nitrite supplementation for healthy arterial aging." Journal of Applied Physiology 116, no. 5 (March 1, 2014): 463–77. http://dx.doi.org/10.1152/japplphysiol.01100.2013.
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Aging is the major risk factor for cardiovascular diseases (CVD). This is attributable primarily to adverse changes in arteries, notably, increases in large elastic artery stiffness and endothelial dysfunction mediated by inadequate concentrations of the vascular-protective molecule, nitric oxide (NO), and higher levels of oxidative stress and inflammation. Inorganic nitrite is a promising precursor molecule for augmenting circulating and tissue NO bioavailability because it requires only a one-step reduction to NO. Nitrite also acts as an independent signaling molecule, exerting many of the effects previously attributed to NO. Results of recent studies indicate that nitrite may be effective in the treatment of vascular aging. In old mice, short-term oral sodium nitrite supplementation reduces aortic pulse wave velocity, the gold-standard measure of large elastic artery stiffness, and ameliorates endothelial dysfunction, as indicated by normalization of NO-mediated endothelium-dependent dilation. These improvements in age-related vascular dysfunction with nitrite are mediated by reductions in oxidative stress and inflammation, and may be linked to increases in mitochondrial biogenesis and health. Increasing nitrite levels via dietary intake of nitrate appears to have similarly beneficial effects in many of the same physiological and clinical settings. Several clinical trials are being performed to determine the broad therapeutic potential of increasing nitrite bioavailability on human health and disease, including studies related to vascular aging. In summary, inorganic nitrite, as well as dietary nitrate supplementation, represents a promising therapy for treatment of arterial aging and prevention of age-associated CVD in humans.
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Reijrink, Melanie, Stefanie A. De Boer, Anniek M. Van Roon, Riemer H. J. A. Slart, Bernadette O. Fernandez, Martin Feelisch, Hiddo J. L. Heerspink, Harry Van Goor, Jan-Luuk Hillebrands, and Douwe J. Mulder. "Plasma Nitrate Levels Are Related to Metabolic Syndrome and Are Not Altered by Treatment with DPP-4 Inhibitor Linagliptin: A Randomised, Placebo-Controlled Trial in Patients with Early Type 2 Diabetes Mellitus." Antioxidants 10, no. 10 (September 29, 2021): 1548. http://dx.doi.org/10.3390/antiox10101548.
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The depletion of nitrate and nitrite, stable nitric oxide (NO) end-products, promotes adipose tissue dysfunction and insulin resistance (IR). Dipeptidyl peptidase-4 (DPP-4) inhibitors have the potentially beneficial side effect of increasing NO availability. In this study, nitrate and nitrite levels and the effects of DPP-4 inhibitor linagliptin were investigated in relation to metabolic syndrome (MetS) markers. Treatment-naive patients with early type 2 diabetes mellitus (T2DM) (n = 40, median age 63 IQR (55–67) years, 63% male, mean HbA1c 45 ± 4.4 mmol/mol) were randomized (1:1) to linagliptin (5 mg/day) or placebo. MetS-related markers (body mass index (BMI), triglycerides, HOMA-IR, gamma-glutamyltransferase (GGT), C-reactive protein (CRP), and adiponectin), plasma levels of nitrate, nitrite, total free thiols (TFT) and vegetable intake were estimated at baseline and after 4 and 26 weeks of treatment. Plasma nitrate, but not nitrite, correlated positively with vegetable intake (r = 0.38, p = 0.018) and was inversely associated with HOMA-IR (r = −0.44, p = 0.006), BMI (r = −0.35, p = 0.028), GGT (r = −0.37, p = 0.019) and CRP (r = −0.34, p = 0.034). The relationship between nitrate and HOMA-IR remained significant after adjusting for BMI, CRP, vegetable intake and GGT. With stable vegetable intake, nitrate and nitrite, TFT, adipokines and CRP did not change after 26 weeks of linagliptin treatment. While plasma nitrate is inversely associated with MetS, linagliptin treatment does not significantly influence nitrate and nitrite concentrations, oxidative stress, adipose tissue function and systemic inflammation.
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Ikonomidis, Ignatios, George Pavlidis, Maria Tsoumani, Foteini Kousathana, Konstantinos Katogiannis, Damianos Tsilivarakis, John Thymis, et al. "Endothelial Dysfunction Is Associated with Decreased Nitric Oxide Bioavailability in Dysglycaemic Subjects and First-Degree Relatives of Type 2 Diabetic Patients." Journal of Clinical Medicine 11, no. 12 (June 9, 2022): 3299. http://dx.doi.org/10.3390/jcm11123299.
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Oxidative stress plays an important role in the pathogenesis of diabetes. We investigated oxidative stress and nitrite/nitrate concentrations at baseline and during postprandial hyperglycaemia in 40 first-degree relatives (FDRs) of diabetic patients with normal oral glucose tolerance test (OGTT) results, 40 subjects with abnormal OGTT results (dysglycaemic) and 20 subjects with normal OGTT results (normoglycaemic). Malondialdehyde (MDA), protein carbonyls (PCs), nitrite/nitrate plasma levels, the perfused boundary region (PBR—Glycocheck) of the sublingual microvessels, a marker of glycocalyx integrity, coronary flow reserve (CFR) and left ventricular global longitudinal strain (GLS) were assessed at 0 and 120 min of the OGTT. Insulin sensitivity was evaluated using Matsuda and the insulin sensitivity index (ISI). In all subjects, there were no significant changes in MDA or PC after the OGTT (p > 0.05). Compared with normoglycaemic subjects, FDRs and dysglycaemic subjects had significantly decreased nitrite/nitrate levels (−3% vs. −24% vs. −30%, respectively), an increased PBR and reduced CFR and GLS at 120 min (p < 0.05). The percent reduction in nitrite/nitrate was associated with abnormal Matsuda and ISI results, reversely related with the percent increase in PBR (r = −0.60) and positively related with the percent decrease in CFR (r = 0.39) and GLS (r = 0.48) (p < 0.05). Insulin resistance is associated with reduced nitric oxide bioavailability and coronary and myocardial dysfunction in FDRs and dysglycaemic subjects.
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Gubina-Vakulyck, G. I., S. A. Denysenko, T. V. Gorbach, Ye M. Zorenko, and V. S. Goydina. "Morphofunctional state of the medulla and the fascicular zone of the adrenal cortex in modeling Alzheimer's disease by excessive administration of sodium nitrite." Morphologia 15, no. 3 (December 25, 2021): 76–83. http://dx.doi.org/10.26641/1997-9665.2021.3.76-83.
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Background. Nitrates and nitrites are found in soil, water, human food, dyes, and medicines. In the literature, both positive and negative effects from the ingestion of nitrates and nitrites into the body are considered. A nitrite model of Alzheimer's type dementia of vascular origin was used in the work. Objective. The aim of the study was to study the morphofunctional state of the adrenal glands of experimental animals with prolonged administration of sodium nitrite. The study was carried out on male rats of the WAG population, which were divided into 3 groups: gr. N-14 - received injections of a water solution of sodium nitrite at a dose of 50 mg / kg of body weight daily for 14 days; gr. N-28 - Rats received similar injections for 28 days. Injections are intraperitoneal. Control rats were injected with 0.9% sodium chloride solution. Results. In animals of the main groups, the formation of a morphofunctional picture of the development of a stress reaction takes place, which was also confirmed morphometrically, and in group N-28 - with signs of incipient decompensation of the medulla and the fascicular zone of the adrenal cortex. Conclusion. When simulating Alzheimer's disease in laboratory rats by the introduction of a water solution of sodium nitrite at a dose of 50 mg / kg of body weight by daily intraperitoneal injection for 14 and 28 days, a picture of their morphofunctional activation is formed in the medulla and fascicular zone of the adrenal cortex. In the group with a 28-day course of administration of sodium nitrite solution, morphofunctional signs of decompensation of the medulla and the fascicular zone of the adrenal glands (especially the medulla) appear, which indicates the development of severe distress in animals and the impossibility of restoring homeostasis.
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Christ, Ricardo, Aleksandro Schafer Da Silva, Mateus Eloir Gabriel, Luan Cleber Henker, Renan Augusto Cechin, Manoela Marchezan Piva, Nathieli Bianchin Bottari, et al. "Cholinesterase Activities and Oxidative Stress in Cattle Experimentally Exposed to Nitrate/Nitrite in Cultivated Pasture with Different Fertilization Schemes." Acta Scientiae Veterinariae 46, no. 1 (April 12, 2018): 9. http://dx.doi.org/10.22456/1679-9216.86680.
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Background: Nitrate and nitrite poisoning is associated with pasture intake that has high nitrate levels and leads to acute methemoglobinemia. Pasture may accumulate nitrate under certain conditions, such as excessively fertilized soil or environmental conditions that enhance the N absorption (rain preceded by a period of drought). After ingestion of plants, this substrate reaches the rumen and, in physiological conditions, is reduced to nitrite and afterward to ammonia. The aim of this study was to evaluate changes in cholinesterase activities and oxidative stress caused by subclinical poisoning for nitrate and nitrite in cattle fed with Pennisetum glaucum in three different fertilization schemes.Materials, Methods & Results: In order to perform the experimental poisoning, the pasture was cultivated in three different paddocks: with nitrogen topdressing (urea; group 1), organic fertilizer (group 2) or without fertilizer (group 3; control). Nitrate accumulation in forage was evaluated by the diphenylamine test. After food fasting of 12 h, nine bovine were randomly allocated to one of the experimental groups and fed with fresh forage (ad libitum) from respective paddock. In different time points from beginning of pasture intake (0, 2, 4, 6 and 9 h) heart rate and respiratory frequency were assessed, as well as mucous membrane color and behavioral changes. Blood samples from jugular vein into vials with and without anticoagulant were collected. From blood samples, serum nitrite levels, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme activity were evaluated, as well as oxidative stress through the following parameters: levels of nitrate/nitrite (NOx ), thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS), beyond the antioxidant system by enzyme activity measurement of catalase (CAT) and superoxide dismutase (SOD). The diphenylamine test was positive to group 1 and 2, so that the pasture presented 3.16 mg/kg, 2.98 mg/kg and 1.67 mg/kg of nitrate for group 1, 2 and 3, respectively. In addition, cows from group 1 demonstrated increased (P < 0.05) nitrite levels in serum, compared to other groups, and greater heart rate after 9 h (P < 0.05). The AChE and BChE activity in group 1 showed significant increase (P < 0.05) at 4 and 6 h (AChE), and 4 and 9 h (BChE) compared to group 3. Also, NOx levels were lower at 6 and 9 h (P < 0.05) and at 9 h (P < 0.05) for animals of group 1 and 2, respectively, when compared to group 3. Furthermore, in the group 1 levels of ROS and TBARS were significantly higher (P < 0.05) after 2 and 4 h, and 6 and 9 h compared to other groups, respectively. The CAT activity increased significantly (P < 0.05) with 2 and 4 h of the experiment, but on the other hand, decreased at 6 and 9 h in group 1. Nevertheless, the animals from group 2 presented only a significant reduction in this enzyme activity at 9 h. Furthermore, SOD activity was reduced in animals of groups 1 (P < 0.05) at 4, 6 and 9 h, compared to other groups.Discussion: It was concluded that the nitrate and nitrite poisoning by pasture intake cultivated and fertilized with urea leads to increased levels of serum nitrite, as well as the cholinesterase activity and causes oxidative stress in cattle. It is conjectured that the cholinesterase activity and oxidative stress may assist in understanding the pathophysiology of changes caused by poisoning.
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Maslakova, A. O., and M. Ya Liuta. "Photobiomodulation therapy protects red blood cells against nitrative stress during streptozotocin-induced diabetes." Studia Biologica 16, no. 3 (October 4, 2022): 3–18. http://dx.doi.org/10.30970/sbi.1603.685.
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Background. According to the International Diabetes Federation Diabetes Atlas, 10th edition, diabetes is responsible for 6.7 million deaths in 2021. Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia secondary to either resistance to insulin, insufficient insulin secretion, or both. Oxidative and nitrative stress is a vital part of the complex mechanism by which diabetes and its complications develop. It is known that Photobiomodulation therapy accelerates diabetic wound healing, treats relegated inflammation, and increases oxygen availability for cells. Although some basic molecular mechanisms caused by photobiomodulation therapy in different cell types are already known, they have not been studied in erythrocytes and are different due to the absence of central organelles such as nucleus and mitochondria. The aim of the study was to investigate the effect of photobiomodulation therapy on the development of nitrative stress in blood plasma and erythrocytes of rats from different experimental groups. Materials and Methods. The study was performed on white outbred male rats weighing 130–180 g. The diabetes mellitus was induced by intraperitoneal injection of streptozotocin (60 mg/kg). Rats were exposed to photobiomodulation with light-emitting diodes at a wavelength of 630–660 nm daily for 10 days. The irradiation time was 5 minutes. The content of nitrite and nitrate anions, total NO synthase activity, as well as the activity of its endothelial and inducible isoforms in red blood cells of rats were determined spectrophotometrically. Results and Discussion. Under streptozotocin-induced diabetes mellitus, the content of nitrite and nitrate anions and NO synthase activity increased in the rats’ red blood cells, as well as in blood plasma. Moreover, we found an increase in inducible NO synthase activity and nitrate ion content in red blood cells of irradiated healthy rats. Also, there was an increase in nitrite and nitrate ion content after photobiomodulation therapy in the blood plasma of healthy animals. On the other hand, irradiation caused a decrease in NO synthase activity with a parallel reduction in both nitrite and nitrate anions content in erythrocytes and blood plasma of rats with experimental diabetes. Conclusion. Photobiomodulation therapy protects rats’ red blood cells from nitrative stress during streptozotocin-induced diabetes mellitus.
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Liu, Xiaochen, Daixia Wang, Yan Shang, Xuee Yu, Baoquan Gao, Jianjian Lv, Jitao Li, Ping Liu, Jian Li, and Xianliang Meng. "Survival, Energy Status, and Cellular Stress Responses of the Juvenile Swimming Crab Portunus trituberculatus under Acute Nitrite Stress." Fishes 8, no. 4 (April 19, 2023): 215. http://dx.doi.org/10.3390/fishes8040215.
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Nitrite is a common pollutant encountered in aquaculture systems. During intensive hatchery, accumulation of nitrite can cause massive mortality of juvenile crustaceans. However, the nitrite toxicity and cellular stress responses in juvenile crustaceans is not clearly understood. Here, we investigate the survival, energy metabolism, and cellular stress responses in juvenile P. trituberculatus, an important aquaculture species in China, under acute nitrite stress. The results revealed nitrite resulted in a significant decrease in survival rate of juvenile swimming crab. After nitrite exposure, the activity of catabolic enzymes, such as HK, PK, CS, and CPT-1, were initially enhanced, and then they showed significant decrease at the late stage of exposure, accompanied by reduction in ATP and adenylate energy charge (AEC). The impaired energy homeostasis was possibly associated with disturbed AMPK signaling and enhanced anaerobic metabolism, which was indicated by the high levels of LDH activity and HIF-1α expression. Furthermore, we found that nitrite stress can depress antioxidant systems and unfold protein responses, causing oxidative damage and endoplasmic reticulum (ER) stress, and this, in turn, can trigger autophagy and apoptosis through both caspase-dependent and caspase-independent pathways. The results of the present study improve our understanding regarding adverse effects of nitrite on P. trituberculatus and provide valuable information for hatchery management.
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Galiniak, Sabina, Marek Biesiadecki, Mateusz Mołoń, Patrycja Olech, and Krzysztof Balawender. "Serum Oxidative and Nitrosative Stress Markers in Clear Cell Renal Cell Carcinoma." Cancers 15, no. 15 (August 7, 2023): 3995. http://dx.doi.org/10.3390/cancers15153995.
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Oxidative stress is believed to be a factor in the development and progression of renal cell carcinoma (RCC). The identification of the oxidative and nitrosative modification of proteins and the definition of their roles in clear cell RCC (ccRCC) may be helpful in the elaboration of targeted therapeutic approaches to mitigate protein damage. This study aimed to investigate the status of oxidative/nitrosative stress and to explore its role in the development and progression. The studied group consisted of 48 newly diagnosed ccRCC and 30 healthy controls. Serum levels of oxidative stress markers—advanced oxidation protein products (AOPP), thiol groups, Amadori reaction products, 3-nitrotyrosine, nitrate/nitrite, malondialdehyde (MDA), 4-hydroxy-2-nonenal and total antioxidant capacity (TAC)—were determined. Additionally, associations between tumour stage assessed according to TNM classification, histological grade, and the effect of the presence of angioinvasion on the level of stress markers were evaluated. The levels of Amadori products, 3-nitrotyrosine, and nitrate/nitrite were elevated, while the levels of thiol groups and TAC decreased in the ccRCC group. The levels of AOPP, Amadori, and 3-nitrotyrosine increased, and thiol groups and TAC levels decreased with the increasing pathological stage of the tumour. In the case of advanced histological assessment of the tumour, we found decreasing levels of thiol groups and increasing levels of MDA. In patients with angioinvasion, nitrate/nitrite and MDA levels were significantly elevated compared to those in patients without angioinvasion. Oxidative stress increased with the progression of the disease assessed according to the TNM and histological grade. These results demonstrate systemic oxidative stress in ccRCC, suggesting the therapeutic application of antioxidants.
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May, James M., Zhi-Chao Qu, Li Xia, and Charles E. Cobb. "Nitrite uptake and metabolism and oxidant stress in human erythrocytes." American Journal of Physiology-Cell Physiology 279, no. 6 (December 1, 2000): C1946—C1954. http://dx.doi.org/10.1152/ajpcell.2000.279.6.c1946.
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Nitric oxide, when released into the bloodstream, is quickly scavenged by Hb in erythrocytes or oxidized to nitrite. Nitrite can also enter erythrocytes and oxidize Hb. The goals of this work were to determine the mechanism of erythrocyte nitrite uptake and whether this uptake causes oxidant stress in these cells. Erythrocytes took up 0.8 mM nitrite with a half-time of 11 min. Nitrite uptake was sensitive to temperature and to the pH and ionic composition of the medium but was not inhibited by the specific anion-exchange inhibitor DIDS. About 25% of nitrite uptake occurred on the sodium-dependent phosphate transporter and the rest as diffusion of nitrous acid or other species across the plasma membrane. Methemoglobin formation increased in proportion to the intracellular nitrite concentration. Nitrite reacted with erythrocyte ascorbate, but ascorbate loading of cells decreased nitrite-induced methemoglobin formation only at high nitrite concentrations. In conclusion, nitrite rapidly enters erythrocytes and reacts with oxyhemoglobin but does not exert a strong oxidant stress on these cells.
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Gratziou, C., N. Rovina, M. Makris, D. C. M. Simoes, A. Papapetropoulos, and C. Roussos. "Breath Markers of Oxidative Stress and Airway Inflammation in Seasonal Allergic Rhinitis." International Journal of Immunopathology and Pharmacology 21, no. 4 (October 2008): 949–57. http://dx.doi.org/10.1177/039463200802100419.
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Oxidative stress (OS) is well documented in asthma, but so far little data has been reported in non-asthmatic patients with Seasonal Allergic Rhinitis (SAR). The aim of this study is to investigate the degree of OS and airway inflammation in patients with SAR, with and without concomitant Asthma (SAR +A), using breath markers in exhaled air and in Exhaled Breath Condensate (EBC). In addition, the effects of natural allergen exposure and intranasal steroid treatment on these markers were evaluated. Exhaled NO (eNO) and CO, combined with measurements of 8-Isoprostane (Iso-8), Leukotriene B4 (LTB4) and nitrate/nitrite in EBC, were performed in 23 patients, 11 with SAR and 12 with SAR+A, and 16 healthy subjects. Iso-8 and LTB4 were significantly increased in both groups of patients (median values 43.6 pg/ml and 138.4 pg/ml in SAR group; 38.9 pg/ml, and 164.6 pg/ml in SAR+A group respectively; p>0.05) compared to healthy subjects (18.6 pg/ml and 7.8 pg/ml; p<0.05). Nitrate/nitrite and eNO levels were elevated in both groups compared to controls, but were significantly higher in the SAR+A compared to SAR group (nitrate/nitrite 9 μM and 3.9 μM; p=0.025; and eNO 18.5 ppb and 12.5 ppb, respectively; p>0.05). Nasal steroids caused significant reduction in LTB4 and 8-isoprostane levels in both groups of patients (p<0.05), while nitrate levels and eNO concentration were little affected by nasal treatment. OS markers were decreased at normal levels out of pollen season. Natural allergen exposure induces OS and airway inflammation, as assessed by measurements of markers in EBC and exhaled air, in patients with SAR who have no clinical signs of lower airway involvement. Besides, intranasal steroid treatment may have a regulatory role in the OS.
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Xu, Zhenkun, Hongzhi Zhang, Meijie Guo, Dan Fang, Jun Mei, and Jing Xie. "Analysis of Acute Nitrite Exposure on Physiological Stress Response, Oxidative Stress, Gill Tissue Morphology and Immune Response of Large Yellow Croaker (Larimichthys crocea)." Animals 12, no. 14 (July 12, 2022): 1791. http://dx.doi.org/10.3390/ani12141791.
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Nitrite is a common pollutant in aquaculture water, and nitrite toxicity that negatively affects aquatic species is common in aquaculture systems when the water quality is low. Therefore, the present research aimed to evaluate the effect of acute nitrite exposure on the hematological parameters, antioxidant enzymes, immune response, and gill morphology of large yellow croaker (Larimichthys crocea). The fish were randomly separated and exposed to four (i.e., 0, 29.36, 58.73, and 88.09 mg/L) nitrite concentrations for 48 h. The fish blood and gills were collected at 0, 12, 24, 36, and 48 h of nitrite exposure for further analysis. In hematological parameters, the results showed that the levels of hemoglobin, triglyceride, and total cholesterol in blood significantly decreased (p < 0.05) in all nitrite-treated samples after 12 h, while the contents of methemoglobin in blood significantly increased (p < 0.05) in these treatments. After 48 h of nitrite exposure, the levels of cortisol in serum showed a 94.5%, 132.1%, and 165.6% increase in fish exposed to 29.36, 58.73, and 88.09 mg/L nitrite, respectively. The nitrite (i.e., 29.36, 58.73, and 88.09 mg/L) exposure significantly increased (p < 0.05) the levels of antioxidant enzymes (i.e., catalase and glutathione) in the gill and serum after 12 h of exposure compared with the control. The lysozyme levels in serum decreased in the nitrite (i.e., 29.36, 58.73, and 88.09 mg/L) exposure samples. It was found that immunoglobulin levels in the 29.36, 58.73, and 88.09 mg/L nitrite-treated samples (i.e., 1.86, 1.58, and 0.74 μg/mL, respectively) were lower than that of the control (2.56 μg/mL). In addition, the surface of the gill lamellae displayed deformation and contraction after 48 h of nitrite, especially in the fish exposed to 88.09 mg/L nitrite. These results indicate that the nitrite exposure induced the oxidative stress, affected the immune response, and changed the gill morphology, leading to nitrite poisoning in large yellow croaker.
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Hirabayashi, Naoki, Hiroshi Tanimura, and Hiroki Yamaue. "Nitrite/Nitrate Oxide and Cytokines Changes in Patients with Surgical Stress." Digestive Diseases and Sciences 50, no. 5 (May 2005): 893–97. http://dx.doi.org/10.1007/s10620-005-2661-2.
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Muñoz-Sánchez, Germán, Lucila A. Godínez-Méndez, Mary Fafutis-Morris, and Vidal Delgado-Rizo. "Effect of Antioxidant Supplementation on NET Formation Induced by LPS In Vitro; the Roles of Vitamins E and C, Glutathione, and N-acetyl Cysteine." International Journal of Molecular Sciences 24, no. 17 (August 24, 2023): 13162. http://dx.doi.org/10.3390/ijms241713162.
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Neutrophil extracellular traps (NETs) require reactive oxygen species (ROS) to eliminate pathogens by inducing oxidative stress. However, this process can also cause tissue damage to the host. Neutrophils contain high concentrations of vitamin C (1.5 mM) compared to the bloodstream (0.1 mM), and this antioxidant can interact with vitamin E and glutathione (GSH) inside the cell to maintain the redox balance. Previous studies have investigated the effect of vitamins E or C and N-acetyl cysteine (NAC) on NET formation, but the interactions of these molecules in neutrophils remain unknown. In this study, we investigated the effect of antioxidants alone and two combinations on NET formation and oxidative stress. Neutrophils were pre-loaded with GSH + NAC or vitamin E + vitamin C + GSH + NAC (termed ALL), and LPS-induced NET formation was assessed using fluorometry and immunofluorescence. Antioxidant effects were evaluated by measuring the total antioxidant capacity (TAC), GSH/GSSG ratio, ROS production, nitrite + nitrate levels, and lipid peroxidation. Our results showed that even low doses of antioxidants are capable of decreasing NETs. Furthermore, the combinations augmented TAC and GSH/GSSG ratio and decreased ROS, nitrites + nitrates, and malondialdehyde (MDA) levels in supplemented neutrophils in vitro.
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Costa-Broseta, Álvaro, MariCruz Castillo, and José León. "Nitrite Reductase 1 Is a Target of Nitric Oxide-Mediated Post-Translational Modifications and Controls Nitrogen Flux and Growth in Arabidopsis." International Journal of Molecular Sciences 21, no. 19 (October 1, 2020): 7270. http://dx.doi.org/10.3390/ijms21197270.
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Plant growth is the result of the coordinated photosynthesis-mediated assimilation of oxidized forms of C, N and S. Nitrate is the predominant N source in soils and its reductive assimilation requires the successive activities of soluble cytosolic NADH-nitrate reductases (NR) and plastid stroma ferredoxin-nitrite reductases (NiR) allowing the conversion of nitrate to nitrite and then to ammonium. However, nitrite, instead of being reduced to ammonium in plastids, can be reduced to nitric oxide (NO) in mitochondria, through a process that is relevant under hypoxic conditions, or in the cytoplasm, through a side-reaction catalyzed by NRs. We use a loss-of-function approach, based on CRISPR/Cas9-mediated genetic edition, and gain-of-function, using transgenic overexpressing HA-tagged Arabidopsis NiR1 to characterize the role of this enzyme in controlling plant growth, and to propose that the NO-related post-translational modifications, by S-nitrosylation of key C residues, might inactivate NiR1 under stress conditions. NiR1 seems to be a key target in regulating nitrogen assimilation and NO homeostasis, being relevant to the control of both plant growth and performance under stress conditions. Because most higher plants including crops have a single NiR, the modulation of its function might represent a relevant target for agrobiotechnological purposes.
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Napolitano, Gaetana, Gianluca Fasciolo, Claudio Agnisola, and Paola Venditti. "Urea Excretion and Arginase Activity as New Biomarkers for Nitrite Stress in Freshwater Aquatic Animals." Water 13, no. 24 (December 9, 2021): 3521. http://dx.doi.org/10.3390/w13243521.
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Background: In recent years, the concern has been growing on increasing aquatic nitrite levels due to anthropogenic activities. Crustaceans and fish easily uptake nitrite via the chloride uptake system of gills. High nitrite body levels may interfere with nitric oxide (NO) production by nitric oxide synthase (NOS). The arginase, which catalyzes arginine conversion to ornithine and urea, is central to NO homeostasis. In vivo, changes in the arginase activity alter urea body levels and urea excretion and modulate NOS by altering arginine availability for NO synthesis. Excess arginase activity may uncouple NOS and induce oxidative stress. Methods: We tested muscle arginase activity and urea excretion in two fish species, zebrafish and convict cichlid, and the crustacean Yamato shrimp, under sub-lethal nitrite stress. Results: Exposure to nitrite (2 mM in the fish, 1 mM in the shrimp) significantly increased blood nitrite concentration in all species. Concomitantly, nitrite stress significantly increased arginase activity, urea excretion, and urea levels in the blood. In Yamato shrimp, urea levels also increased in muscle. Conclusion: Our results agree with the hypothesis that nitrite stress affects NO homeostasis by arginase stimulation and urea excretion. These parameters might function as markers of sub-lethal nitrite stress in freshwater fish and crustaceans.
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Wu, Fan, Xiaobo Sun, Xingfeng Hu, Bingzhang Zou, Nengqing Lin, Jingquan Lin, and Kongshu Ji. "Response of Nitrogen Metabolism in Masson Pine Needles to Elevated CO2." Forests 11, no. 4 (April 1, 2020): 390. http://dx.doi.org/10.3390/f11040390.
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To explore the response of nitrogen metabolism in Masson pine (Pinus massoniana) to high CO2 concentrations, needles from one-year-old seedlings were used as materials to detect key enzyme activities, gene expression and different forms of nitrogen metabolites after CO2 stress for different durations (0 h, 6 h, 12 h, 24 h). The results show that elevated CO2 affected the efficiency of nitrogen metabolism in Masson pine needles, inhibiting the expression of key genes involved in nitrogen metabolism, including glutamate synthase (GOGAT), nitrite reductase (NiR), glutamine synthase (GS), nitrate reductase (NR) and glutamate dehydrogenase (GDH), and decreasing the activities of GOGAT, NiR, and GS. The decrease in enzyme activities and gene expression caused a decrease in different forms of nitrogen metabolites, including total nitrogen, ammonium, nitrite and specific amino acids. With prolonged stress, the nitrate content increased first and then decreased. In this study, the response pattern of nitrogen metabolism to CO2 stress in Masson pine needles was described, which may aid future research on nitrogen utilization in Masson pine.
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Gamal, Maha, Zainab Abdel Wahab, Mohamed Eshra, Laila Rashed, and Nivin Sharawy. "Comparative Neuroprotective Effects of Dexamethasone and Minocycline during Hepatic Encephalopathy." Neurology Research International 2014 (2014): 1–8. http://dx.doi.org/10.1155/2014/254683.
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Objective.Encephalopathy and brain edema are serious complications of acute liver injury and may lead to rapid death of patients. The present study was designed to investigate the role of the inflammatory mediators and oxidative stress in the cytotoxic brain oedema and the neuroprotective effects of both minocycline and dexamethasone.Methods.48 male albino rats were divided into 4 groups: control group, acute liver injury (ALI) group, minocycline pretreated ALI group, and dexamethasone pretreated ALI group. 24 hours after acute liver injury serum ammonia, liver enzymes, brain levels of heme oxygenase-1 gene, iNOS gene expression, nitrite/nitrate, and cytokines were measured. In addition, the grades of encephalopathy and brain water content were assessed.Results.ALI was associated with significant increases in all measured inflammatory mediators, oxidative stress, iNOS gene expression, and nitrite/nitrate. Both minocycline and dexamethasone significantly modulated the inflammatory changes and the oxidative/nitrosative stress associated with ALI. However, only minocycline but not dexamethasone significantly reduced the cytotoxic brain oedema.Conclusion.Both minocycline and dexamethasone could modulate inflammatory and oxidative changes observed in brain after ALI and could be novel preventative therapy for hepatic encephalopathy episodes.
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Hu, Zhenyi, Chenglong Qi, Chenzhi Lin, and Rong Tang. "Nitrite Stress Induces Oxidative Stress and Leads to Muscle Quality Decreased in Wuchang Bream (Megalobrama amblycephala Yih) Juveniles." Water 14, no. 2 (January 8, 2022): 160. http://dx.doi.org/10.3390/w14020160.
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To determine the effects of nitrite exposure on muscle quality and physiological functions in Wuchang bream (Megalobrama amblycephala), we exposed M. amblycephala juveniles to acute nitrite (0, 1, 5, 10, 20 mg/L), and the muscle and blood samples were measured at 12, 24, 48, and 96 h. The results showed that when exposed to nitrite for 12 h, the concentrations of blood glucose, cortisol, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the 20 mg/L experimental group had the maximum value. The activity of lactate dehydrogenase (LDH) increased significantly in a dose-dependently manner and peaked at 96 h in the 20 mg/L group. During 96 h of exposure to nitrite, the total antioxidant capacity (T-AOC) and catalase (CAT) activity in the liver of the 20 mg/L experimental group were significantly higher than those of the control group, while the concentration of muscle glycogen showed a downtrend. At 12 h and 96 h, the hardness of the four experimental groups were significantly higher than that of the control group. Our research shows that acute sodium nitrite exposure will not only cause oxidative stress and decreased muscle quality in M. amblycephala juveniles but also will be accompanied by changes in serum biochemical index, liver antioxidant capacity, muscle physiological characteristics, and muscle physical characteristics. Preliminary speculation may be that acute nitrite exposure may cause M. amblycephala juveniles to choose to reduce muscle quality and activate antioxidant systems.
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Kanzelmeyer, Nele Kirsten, Lars Pape, Kristine Chobanyan-Jürgens, Dimitrios Tsikas, Hans Hartmann, Anne-Jule Fuchs, Bernhard Vaske, et al. "L-Arginine/NO Pathway Is Altered in Children with Haemolytic-Uraemic Syndrome (HUS)." Oxidative Medicine and Cellular Longevity 2014 (2014): 1–9. http://dx.doi.org/10.1155/2014/203512.
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The haemolytic uraemic syndrome (HUS) is the most frequent cause of acute renal failure in childhood. We investigated L-arginine/NO pathway in 12 children with typical HUS and 12 age-matched healthy control subjects. Nitrite and nitrate, the major NO metabolites in plasma and urine, asymmetric dimethylarginine (ADMA) in plasma and urine, and dimethylamine (DMA) in urine were determined by GC-MS and GC-MS/MS techniques. Urinary measurements were corrected for creatinine excretion. Plasma nitrate was significantly higher in HUS patients compared to healthy controlsP=0.021, whereas urine nitrate was borderline lower in HUS patients compared to healthy controlsP=0.24. ADMA plasma concentrations were insignificantly lower, but urine ADMA levels were significantly lower in the HUS patientsP=0.019. Urinary DMA was not significantly elevated. In HUS patients, nitrateR=0.91but not nitrite, L-arginine, or ADMA concentrations in plasma correlated with free haemoglobin concentration. Our results suggest that both NO production and ADMA synthesis are decreased in children with typical HUS. We hypothesize that in the circulation of children with HUS a vicious circle between the L-arginine/NO pathway and free haemoglobin-mediated oxidative stress exists. Disruption of this vicious circle by drugs that release NO and/or sulphydryl groups-containing drugs may offer new therapeutic options in HUS.
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Vine, Claire E., and Jeffrey A. Cole. "Nitrosative stress in Escherichia coli: reduction of nitric oxide." Biochemical Society Transactions 39, no. 1 (January 19, 2011): 213–15. http://dx.doi.org/10.1042/bst0390213.
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The ability of enteric bacteria to protect themselves against reactive nitrogen species generated by their own metabolism, or as part of the innate immune response, is critical to their survival. One important defence mechanism is their ability to reduce NO (nitric oxide) to harmless products. The highest rates of NO reduction by Escherichia coli K-12 were detected after anaerobic growth in the presence of nitrate. Four proteins have been implicated as catalysts of NO reduction: the cytoplasmic sirohaem-containing nitrite reductase, NirB; the periplasmic cytochrome c nitrite reductase, NrfA; the flavorubredoxin NorV and its associated oxidoreductase, NorW; and the flavohaemoglobin, Hmp. Single mutants defective in any one of these proteins and even the mutant defective in all four proteins reduced NO at the same rate as the parent. Clearly, therefore, there are mechanisms of NO reduction by enteric bacteria that remain to be characterized. Far from being minor pathways, the currently unknown pathways are adequate to sustain almost optimal rates of NO reduction, and hence potentially provide significant protection against nitrosative stress.
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Polhemus, David J., Jessica M. Bradley, Kazi N. Islam, Luke P. Brewster, John W. Calvert, Ya-Xiong Tao, Carlos C. Chang, Iraklis I. Pipinos, Traci T. Goodchild, and David J. Lefer. "Therapeutic potential of sustained-release sodium nitrite for critical limb ischemia in the setting of metabolic syndrome." American Journal of Physiology-Heart and Circulatory Physiology 309, no. 1 (July 1, 2015): H82—H92. http://dx.doi.org/10.1152/ajpheart.00115.2015.
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Nitrite is a storage reservoir of nitric oxide that is readily reduced to nitric oxide under pathological conditions. Previous studies have demonstrated that nitrite levels are significantly reduced in cardiovascular disease states, including peripheral vascular disease. We investigated the cytoprotective and proangiogenic actions of a novel, sustained-release formulation of nitrite (SR-nitrite) in a clinically relevant in vivo swine model of critical limb ischemia (CLI) involving central obesity and metabolic syndrome. CLI was induced in obese Ossabaw swine ( n = 18) by unilateral external iliac artery deployment of a full cross-sectional vessel occlusion device positioned within an endovascular expanded polytetrafluoroethylene-lined nitinol stent-graft. At post-CLI day 14, pigs were randomized to placebo ( n = 9) or SR-nitrite (80 mg, n = 9) twice daily by mouth for 21 days. SR-nitrite therapy increased nitrite, nitrate, and S-nitrosothiol in plasma and ischemic skeletal muscle. Oxidative stress was reduced in ischemic limb tissue of SR-nitrite- compared with placebo-treated pigs. Ischemic limb tissue levels of proangiogenic growth factors were increased following SR-nitrite therapy compared with placebo. Despite the increases in cytoprotective and angiogenic signals with SR-nitrite therapy, new arterial vessel formation and enhancement of blood flow to the ischemic limb were not different from placebo. Our data clearly demonstrate cytoprotective and proangiogenic signaling in ischemic tissues following SR-nitrite therapy in a very severe model of CLI. Further studies evaluating longer-duration nitrite therapy and/or additional nitrite dosing strategies are warranted to more fully evaluate the therapeutic potential of nitrite therapy in peripheral vascular disease.
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Raat, Nicolaas J., Audrey C. Noguchi, Virginia Liu, Nalini Raghavachari, Delong Liu, Xiuli Xu, Sruti Shiva, Peter M. Munson, and Mark T. Gladwin. "P52. Dietary nitrate and nitrite modulate the cellular response to ischemic stress." Nitric Oxide 19 (2008): 55. http://dx.doi.org/10.1016/j.niox.2008.06.149.
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Gào, Xīn, Yang Xuan, Axel Benner, Ankita Anusruti, Hermann Brenner, and Ben Schöttker. "Nitric Oxide Metabolites and Lung Cancer Incidence: A Matched Case-Control Study Nested in the ESTHER Cohort." Oxidative Medicine and Cellular Longevity 2019 (September 2, 2019): 1–9. http://dx.doi.org/10.1155/2019/6470950.
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Studies suggest that nitric oxide (NO) may have a possible role in lung carcinogenesis. This study is aimed to evaluate the association of the NO metabolites, namely, nitrite and nitrate, with lung cancer incidence. We conducted a matched case-control study (n=245 incident lung cancer cases and n=735 controls) based on the German ESTHER cohort (n=9,940). Controls were matched to cases on age, sex, smoking status (never/former/current smoking), and pack-years of smoking. The sum of nitrite and nitrate was measured in urine samples using a colorimetric assay and was standardized for renal function by urinary creatinine. Conditional logistic regression models, adjusted for lifestyle factors, asthma prevalence, and family history of lung cancer, were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI). Among incident lung cancer cases, high nitrite/nitrate levels were statistically significantly associated with current smoking, a low BMI, and the oxidative stress biomarker 8-isoprostane levels. Nitrite/nitrate levels in the top quintile were statistically significantly associated with lung cancer incidence: the OR (95% CI) was 1.37 (1.04-1.82) for comparison with the bottom quintile. This association was unaltered after additional adjustment for 8-isoprostane levels and C-reactive protein (CRP). In conclusion, this large cohort study suggested that subjects with high urinary nitrite/nitrate concentrations had an increased risk of lung cancer and this association was independent of smoking, CRP, 8-isoprostane levels, and other established lung cancer risk factors. Further studies are needed to validate these findings and to confirm the hypothesis that pathologically high levels of NO are involved in lung cancer development.
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Famitafreshi, Hamidreza, and Morteza Karimian. "Social State Influences Memory in Novel Object Recognition Test Through Oxidative Stress Balance in Male Rats." Open Pharmacology Journal 8, no. 1 (May 31, 2018): 1–9. http://dx.doi.org/10.2174/1874143601808010001.
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Objective:Social isolation is associated with adverse effects on brain functions. According to previous studies, the reduction of oxidative stress improves cognitive functions. Memory performance is dependent on hippocampus and prefrontal function. The aim of this study is to show that impairment of memory in object recognition test in isolation state is accompanied by deregulation of oxidative stress balance in related areas.Methods and Materials:In this study, 14 male Sprague-Dawley rats were randomly divided into two groups as follows: social and isolation. Socialization and isolation plus one week of acclimatization occurred for fourteen days. At the end of the study, after performing behavioral test, (novel object recognition test) rats were anesthetized and sacrificed. After preparation of tissues in controlled condition, oxidative stress status in hippocampus and prefrontal cortex for Malondialdehyde (MDA), glutathione and nitrite/nitrate was assessed.Results:MDA in the hippocampus and prefrontal cortex was higher in isolated rats compared to social rats. Glutathione and nitrite/nitrate in the hippocampus and prefrontal cortex were lower in isolated rats compared to social rats. Memory performance in novel object recognition test both in short term and long term was better in social rats.Conclusion:Memory performance in novel object recognition test is influenced by social and oxidative stress status. So improving memory is possible through socialization and improvement of antioxidant status.
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Pimková, Kristýna, Leona Chrastinová, Jiří Suttnar, Jana Štikarová, Roman Kotlín, Jaroslav Čermák, and Jan Evangelista Dyr. "Plasma Levels of Aminothiols, Nitrite, Nitrate, and Malondialdehyde in Myelodysplastic Syndromes in the Context of Clinical Outcomes and as a Consequence of Iron Overload." Oxidative Medicine and Cellular Longevity 2014 (2014): 1–10. http://dx.doi.org/10.1155/2014/416028.
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The role of oxidative stress in the initiation and progression of myelodysplastic syndromes (MDS) as a consequence of iron overload remains unclear. In this study we have simultaneously quantified plasma low-molecular-weight aminothiols, malondialdehyde, nitrite, and nitrate and have studied their correlation with serum iron/ferritin levels, patient treatment (chelation therapy), and clinical outcomes. We found significantly elevated plasma levels of total, oxidized, and reduced forms of cysteineP<0.001, homocysteineP<0.001, and cysteinylglycineP<0.006and significantly depressed levels of total and oxidized forms of glutathioneP<0.03and nitriteP<0.001in MDS patients compared to healthy donors. Moreover, total(P=0.032)and oxidized cysteinylglycine(P=0.029)and nitrite(P=0.021)differed significantly between the analyzed MDS subgroups with different clinical classifications. Malondialdehyde levels in plasma correlated moderately with both serum ferritin levels(r=0.78, P=0.001)and serum free iron levels(r=0.60, P=0.001)and were significantly higher in patients with iron overload. The other analyzed compounds lacked correlation with iron overload (represented by serum iron/ferritin levels). For the first time our results have revealed significant differences in the concentrations of plasma aminothiols in MDS patients, when compared to healthy donors. We found no correlation of these parameters with iron overload and suggest the role of oxidative stress in the development of MDS disease.
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Honoré, Jean-Claude, Amna Kooli, Xin Hou, David Hamel, José Carlos Rivera, Émilie Picard, Pierre Hardy, et al. "Sustained hypercapnia induces cerebral microvascular degeneration in the immature brain through induction of nitrative stress." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 298, no. 6 (June 2010): R1522—R1530. http://dx.doi.org/10.1152/ajpregu.00807.2009.
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Hypercapnia is regularly observed in chronic lung disease, such as bronchopulmonary dysplasia in preterm infants. Hypercapnia results in increased nitric oxide synthase activity and in vitro formation of nitrates. Neural vasculature of the immature subject is particularly sensitive to nitrative stress. We investigated whether exposure to clinically relevant sustained high CO2 causes microvascular degeneration in the newborn brain by inducing nitrative stress, and whether this microvascular degeneration has an impact on brain growth. Newborn rat pups were exposed to 10% CO2 as inspired gas (PaCO2 = 60–70 mmHg) starting within 24 h of birth until postnatal day 7 (P7). Brains were notably collected at different time points to measure vascular density, determine brain cortical nitrite/nitrate, and trans-arachidonic acids (TAAs; products of nitration) levels as effectors of vessel damage. Chronic exposure of rat pups to high CO2 (PaCO2 ≈ 65 mmHg) induced a 20% loss in cerebrovascular density at P3 and a 15% decrease in brain mass at P7; at P30, brain mass remained lower in CO2-exposed animals. Within 24 h of exposure to CO2, brain eNOS expression and production of nitrite/nitrate doubled, lipid nitration products (TAAs) increased, and protein nitration (3-nitrotyrosine immunoreactivity) was also coincidently augmented on brain microvessels (lectin positive). Intracerebroventricular injection of TAAs (10 μM) replicated cerebrovascular degeneration. Treatment of rat pups with NOS inhibitor (l-Nω-nitroarginine methyl ester) or a peroxynitrite decomposition catalyst (FeTPPS) prevented hypercapnia-induced microvascular degeneration and preserved brain mass. Cytotoxic effects of high CO2 were reproduced in vitro /ex vivo on cultured endothelial cells and sprouting microvessels. In summary, hypercapnia at values frequently observed in preterm infants with chronic lung disease results in increased nitrative stress, which leads to cerebral cortical microvascular degeneration and curtails brain growth.
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Lee, Jae Won, Ee Taek Hwang, and Jin Soo Han. "Protective Effects of Topical Application of Nitrite on Testicular Ischemia-Reperfusion Injury in Rats." Oxidative Medicine and Cellular Longevity 2021 (June 26, 2021): 1–10. http://dx.doi.org/10.1155/2021/5514537.
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Testicular torsion is a urologic emergency induced by torsion of the spermatic cord, interrupting blood circulation to the testis. Therapeutic options for testicular torsion, except surgical restoration of testis, are rarely applied in clinical practice. This study, therefore, investigated whether topical application of nitrite (NO2-) is beneficial in tissue damage due to testicular ischemia-reperfusion (I/R) injury in rats. Pubertal Sprague-Dawley rats were assigned to seven groups: group A, sham-operated control group; group B, I/R with no treatment; groups C, D, and E, I/R followed by treatment with three different doses of nitrite; group F, I/R followed by administration of nitrite and a NO scavenger, C-PTIO (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt); and group G, I/R followed by administration of nitrate (NO3-). Unilateral testicular ischemia was maintained for 5 h, followed by reperfusion for 24 h. Nitrite and nitrate were topically administered before reperfusion. Compared to group A, germ cell apoptosis, oxidative stress, antioxidant enzymatic function, and lipid peroxidation were significantly increased, along with abnormal morphology and impaired spermatogenesis in group B ( P < 0.05 ). In contrast, testicular damage was generally attenuated in the nitrite treatment groups due to a reduction in superoxide and peroxynitrite levels and the inhibition of caspase-3-dependent apoptosis ( P < 0.05 vs. group B). These therapeutic effects of nitrite-derived NO were suppressed after injection of C-PTIO, which showed in group F. Taken together, our results demonstrate that topical application of nitrite may be one of the therapeutic strategies for testicular ischemia-reperfusion injury.
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Trautwein, Kathleen, Simon Kühner, Lars Wöhlbrand, Thomas Halder, Kenny Kuchta, Alexander Steinbüchel, and Ralf Rabus. "Solvent Stress Response of the Denitrifying Bacterium “Aromatoleum aromaticum” Strain EbN1." Applied and Environmental Microbiology 74, no. 8 (February 8, 2008): 2267–74. http://dx.doi.org/10.1128/aem.02381-07.
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ABSTRACT The denitrifying betaproteobacterium “Aromatoleum aromaticum” strain EbN1 degrades several aromatic compounds, including ethylbenzene, toluene, p-cresol, and phenol, under anoxic conditions. The hydrophobicity of these aromatic solvents determines their toxic properties. Here, we investigated the response of strain EbN1 to aromatic substrates at semi-inhibitory (about 50% growth inhibition) concentrations under two different conditions: first, during anaerobic growth with ethylbenzene (0.32 mM) or toluene (0.74 mM); and second, when anaerobic succinate-utilizing cultures were shocked with ethylbenzene (0.5 mM), toluene (1.2 mM), p-cresol (3.0 mM), and phenol (6.5 mM) as single stressors or as a mixture (total solvent concentration, 2.7 mM). Under all tested conditions impaired growth was paralleled by decelerated nitrate-nitrite consumption. Additionally, alkylbenzene-utilizing cultures accumulated poly(3-hydroxybutyrate) (PHB) up to 10% of the cell dry weight. These physiological responses were also reflected on the proteomic level (as determined by two-dimensional difference gel electrophoresis), e.g., up-regulation of PHB granule-associated phasins, cytochrome cd1 nitrite reductase of denitrification, and several proteins involved in oxidative (e.g., SodB) and general (e.g., ClpB) stress responses.
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Bradley, Jessica M., Kazi N. Islam, David J. Polhemus, Erminia Donnarumma, Luke P. Brewster, Ya-Xiong Tao, Traci T. Goodchild, and David J. Lefer. "Sustained release nitrite therapy results in myocardial protection in a porcine model of metabolic syndrome with peripheral vascular disease." American Journal of Physiology-Heart and Circulatory Physiology 309, no. 2 (July 15, 2015): H305—H317. http://dx.doi.org/10.1152/ajpheart.00163.2015.
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Metabolic syndrome (MetS) reduces endothelial nitric oxide (NO) bioavailability and exacerbates vascular dysfunction in patients with preexisting vascular diseases. Nitrite, a storage form of NO, can mediate vascular function during pathological conditions when endogenous NO is reduced. The aims of the present study were to characterize the effects of severe MetS and obesity on dyslipidemia, myocardial oxidative stress, and endothelial NO synthase (eNOS) regulation in the obese Ossabaw swine (OS) model and to examine the effects of a novel, sustained-release formulation of sodium nitrite (SR-nitrite) on coronary vascular reactivity and myocardial redox status in obese OS subjected to critical limb ischemia (CLI). After 6 mo of an atherogenic diet, obese OS displayed a MetS phenotype. Obese OS had decreased eNOS functionality and NO bioavailability. In addition, obese OS exhibited increased oxidative stress and a significant reduction in antioxidant enzymes. The efficacy of SR-nitrite therapy was examined in obese OS subjected to CLI. After 3 wk of treatment, SR-nitrite (80 mg·kg−1·day−1 bid po) increased myocardial nitrite levels and eNOS function. Treatment with SR-nitrite reduced myocardial oxidative stress while increasing myocardial antioxidant capacity. Ex vivo assessment of vascular reactivity of left anterior descending coronary artery segments demonstrated marked improvement in vasoreactivity to sodium nitroprusside but not to substance P and bradykinin in SR-nitrite-treated animals compared with placebo-treated animals. In conclusion, in a clinically relevant, large-animal model of MetS and CLI, treatment with SR-nitrite enhanced myocardial NO bioavailability, attenuated oxidative stress, and improved ex vivo coronary artery vasorelaxation.
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Fernandes, Monique Carolina Nunes, Flávia Barbosa Silva Botelho, Kamila Rezende Dázio de Souza, Gabrielle Carvalho Pereira, Camila Soares Cardoso da Silva, and Douglas Goulart Castro. "ATIVIDADE DA ENZIMA NITRATO REDUTASE EM ARROZ DE TERRAS ALTAS SOB CONDIÇÕES DE ESTRESSE HÍDRICOS." Nativa 8, no. 4 (July 31, 2020): 484–89. http://dx.doi.org/10.31413/nativa.v8i4.9707.
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A assimilação de nitrogênio é um processo vital que controla o crescimento e desenvolvimento da planta, garantindo bons níveis de produtividade de grãos. A enzima nitrato redutase (NR) catalisa o primeiro passo enzimático da assimilação de nitrogênio pelas plantas superiores por meio da redução do nitrato (NO3-) a nitrito (NO2-). Assim, objetivou-se estudar a atividade da enzima redutase do nitrato em genótipos de arroz de terras altas e correlacioná-la com os demais caracteres agronômicos. O experimento foi conduzido em dois ambientes distintos, com e sem irrigação suplementar. As análises de atividade enzimática foram realizadas em laboratório. Foram avaliados 20 genótipos de um experimento de VCU na safra 2014/2015. O delineamento experimental foi em blocos casualizados com três repetições. Foi obtida a quantidade de nitrito liberado pelos tecidos vegetais na solução de incubação (µmoles NO2- gmf -1 h-1) em sete coletas realizadas aos 7, 14, 21, 28, 45, 75 e 100 dias após emergência (DAE), sempre no período da manhã, em todas as parcelas. Diante dos resultados, observou-se que a atividade da enzima NR, na cultura do arroz, é dependente do genótipo, do período de desenvolvimento vegetal e das condições ambientais, sendo de maior expressão no início do ciclo da cultura e em ambientes sem a ocorrência de estresse hídrico. A atividade da enzima RN não deve ser utilizada isoladamente para seleção indireta no caráter produtividade na cultura do arroz de terras altas, é necessário avaliar outras características que complementem à seleção.Palavras-chave: Oryza sativa; nitrogênio; melhoramento de plantas; expressão enzimática. ACTIVITY OF THE NITRATE REDUCTASE ENZYME IN UPLAND RICE UNDER WATER STRESS CONDITIONS ABSTRACT:Nitrogen uptake is a vital process that controls plant growth and development, ensuring great grain yield levels. The enzyme nitrate reductase (NR) catalyzes the first enzymatic step of nitrogen uptake by higher plants by reducing nitrate (NO3-) to nitrite (NO2-). Thus, the objective was to study the activity of nitrate reductase enzyme in upland rice genotypes and to correlate it with other agronomic traits. The experiment was conducted in two distinct environments, with and without supplemental irrigation. The enzymatic activity assays were performed in the laboratory. Twenty genotypes of a VCU experiment in the 2014/2015 crop were evaluated. The experimental design was in randomized blocks with three replications. The amount of nitrite released by the plant tissues in the incubation solution (µmoles NO2-gmf -1 h-1) was obtained in seven collections performed at 7, 14, 21, 28, 45, 75 and 100 days after emergence (DAE). always in the mornings, in all installments. Given the results, it was observed that the activity of NR enzyme in rice culture is dependent on genotype, plant development period and environmental conditions, being more expressive at the beginning of the crop cycle and in environments without occurrence of water stress. The activity of the RN enzyme should not be used alone for indirect selection in the productivity character in the upland rice crop, it is necessary to evaluate other characteristics that complement the selection.Keywords: Oryza sativa; nitrogen; plant breeding; enzymatic expression.
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Hsu, Dur-Zong, Ya-Hui Li, Pei-Yi Chu, Srinivasan Periasamy, and Ming-Yie Liu. "Sesame Oil Prevents Acute Kidney Injury Induced by the Synergistic Action of Aminoglycoside and Iodinated Contrast in Rats." Antimicrobial Agents and Chemotherapy 55, no. 6 (March 14, 2011): 2532–36. http://dx.doi.org/10.1128/aac.01597-10.
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ABSTRACTThe aim of the study was to investigate the effect of sesame oil on acute kidney injury induced by the synergistic action of aminoglycoside and iodinated contrast in rats. Acute kidney injury was induced by a 5-day course of daily gentamicin injections (100 mg/kg of body weight, subcutaneously) and then iodinated contrast (4 ml/kg, intravenously) in male specific-pathogen-free Sprague-Dawley rats. Sesame oil (0.5 ml/kg, orally) was given 1 h before iodinated contrast. Renal function and oxidative stress were assessed 6 h after iodinated contrast injection. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. Renal oxidative stress was assessed by determining renal lipid peroxidation, myeloperoxidase, hydroxyl radical, superoxide anion, nitrite/nitrate, and inducible nitric oxide synthase levels. Sesame oil significantly prevented the rise of serum blood urea nitrogen and creatinine levels. Furthermore, there was a parallel inhibition of the rise in levels of expression of renal lipid peroxidation, myeloperoxidase, hydroxyl radicals, superoxide anion, nitrite/nitrate, and inducible nitric oxide synthase in rats with gentamicin-plus-iodinated contrast-induced acute kidney injury. We conclude that sesame oil may attenuate aminoglycoside-plus-iodinated contrast-induced acute kidney injury by inhibiting renal oxidative stress in rats.
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Krishna Rao, R., and A. Gnanam. "Inhibition of nitrate and nitrite reductase activities by salinity stress in Sorghum vulgare." Phytochemistry 29, no. 4 (January 1990): 1047–49. http://dx.doi.org/10.1016/0031-9422(90)85400-a.
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Durzand, D. "Stress-induced nitric oxide and adaptive plasticity in conifers." Journal of Forest Science 48, No. 7 (May 20, 2019): 281–91. http://dx.doi.org/10.17221/11888-jfs.
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The excitable properties of conifer protoplasm consist of nitric oxide (NO) bursts that prime and prepare chemical messengers for the transmission of stressful environmental signals. NO in somatic and reproductive cells is produced in response to mechanical forces, gravity, wounding, changes in nutrition, hypoxia, drought, salinity, temperature shock, pollutants, and <br /> pathogen attack. NO arises primarily from nitrite via nitrite:nitric oxide reductase and nitrate reductase. It also arises from arginine N and oxygen via putative nitric oxide synthase activity. NO rapidly reacts with, oxygen species, hemes, thiols, and proteins to produce biochemical signals that directly and indirectly regulate enzymatic activity. The effects of NO depend on its location and concentration. Beneficial reactions counteract oxidative and nitrosative stresses, while damaging reactions, due to high levels of NO, cause oxidative and nitrosative damage, and cell death. NO contributes to structural and functional adaptive plasticity, and to the habituation of trees to their sites. The use of NO donors and traps, and enzyme inhibitors offers a new experimental approach and countermeasures to control stress signals throughout conifer life histories.
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Reddy, C. Prabhakar, Uday Kumar Chiranjeevi, Chandrasekhar N., Kiran Kishore K., and Kishan P. V. "Correlation between endothelial dysfunction, inflammatory status, oxidative stress and total (nitrite/ nitrate) in subjects with diabetes mellitus type 2." International Journal of Basic & Clinical Pharmacology 6, no. 10 (September 23, 2017): 2317. http://dx.doi.org/10.18203/2319-2003.ijbcp20174157.
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Background: Diabetes Mellitus is a systemic metabolic disorder associated with Endothelial dysfunction and increased systemic inflammatory state with oxidative stress leading to increased Cardiovascular risk. This study planned to correlate the level of Endothelial dysfunction with oxidative stress and inflammatory status.Methods: Study was conducted in 60 Diabetes Mellitus subjects of both genders with duration of more than two years. Endothelial dysfunction assessed as Augmentation Pressure and Augmentation Index generated from Radial artery waveforms by tonometer using Spygmocor PWA system. Plasma Total Nitrite/ Nitrate, High sensitive C - Reactive Protein, Malondialdehyde and Glutathione were measured.Results: Out of total 60 Diabetes Mellitus subjects 16 subjects were with Coronary Artery Disease. There was no significant difference in High sensitive C - Reactive Protein, Glutathione, Malondialdehyde and Total Nitrite/ Nitrate between Diabetes Mellitus with Coronary Artery Disease and without Coronary Artery Disease, however significant difference (p=0.02) was observed Augmentation Pressure between Diabetic alone (12.8±5.19 mm of Mercury) and diabetics with Coronary Artery Disease (16.13±33.47 mm of Mercury) and Augmentation Index (p=0.04) between Diabetic alone (29.8±5.68 mm of Mercury) and diabetics with Coronary Artery Disease (40.01±5.74). As endothelial function is age dependent the subjects were divided into three age groups (20-40 years, 40-60 years and more than 60 years). High sensitive C - Reactive Protein, Glutathione, Malondialdehyde, Total Nitrite/ Nitrate and Augmentation Index did not differ in the three age groups while Augmentation Pressure (p=0.0096) showed significant difference between age group 20-40 years (10.59±3.24) and age group more than 60 years (15.83±3.92).Conclusions: There is significant endothelial dysfunction observed in Diabetes Mellitus subjects and Diabetes Mellitus with coronary artery disease showed greater endothelial dyfunction. Thereby concluding that Diabetes Mellitus subjects were at higher risk for development of coronary artery disease and as endothelial dysfunction is an early event, it may have some prognostic value.
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Kim, Jun-Hwan, Yue Jai Kang, and Kyung Mi Lee. "Effects of Nitrite Exposure on the Hematological Properties, Antioxidant and Stress Responses of Juvenile Hybrid Groupers, Epinephelus lanceolatus ♂ × Epinephelus fuscoguttatus ♀." Antioxidants 11, no. 3 (March 14, 2022): 545. http://dx.doi.org/10.3390/antiox11030545.
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Nitrite concentrations can reach high levels in indoor aquaculture systems, thus it is vital to determine the nitrite tolerance of aquaculture fish species. Here, juvenile hybrid groupers (Epinephelus lanceolatus ♂ × Epinephelus fuscoguttatus ♀, Family: Serranidae) were exposed to waterborne nitrite at 0, 10, 20, 40, and 80 mg NO2−/L for 2 weeks. Nitrite exposure caused significant reductions in hematocrit and hemoglobin levels, significant increases in plasma calcium and plasma ALP levels, but had no significant effects on magnesium and total protein levels. Of the antioxidant responses investigated, SOD activity increased significantly in the liver and gills, but GST activity and GSH levels were significantly inhibited by nitrite exposure. Stress indicators, such as plasma cortisol and HSP 70 levels, were significantly stimulated by nitrite exposure. In brief, nitrite exposure over 20 mg NO2−/L had toxic effects and affected the hematological properties, antioxidant responses, and stress indicators of juvenile hybrid groupers.
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Godbole, Anjali S., Xiao Lu, Xiaomei Guo, and Ghassan S. Kassab. "NADPH oxidase has a directional response to shear stress." American Journal of Physiology-Heart and Circulatory Physiology 296, no. 1 (January 2009): H152—H158. http://dx.doi.org/10.1152/ajpheart.01251.2007.
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Vessel regions with predilection to atherosclerosis have negative wall shear stress due to flow reversal. The flow reversal causes the production of superoxides (O2−), which scavenge nitric oxide (NO), leading to a decrease in NO bioavailability and endothelial dysfunction. Here, we implicate NADPH oxidase as the primary source of O2− during full flow reversal. Nitrite production and the degree of vasodilation were measured in 46 porcine common femoral arteries in an ex vivo system. Nitrite production and vasodilation were determined before and after the inhibition of NADPH oxidase, xanthine oxidase, or mitochondrial oxidase. NADPH oxidase inhibition with gp91ds-tat or apocynin restored nitrite production and vasodilation during reverse flow. Xanthine oxidase inhibition increased nitrite production at the highest flow rate, whereas mitochondrial oxidase inhibition had no effect. These findings suggest that the NADPH oxidase system can respond to directional changes of flow and is activated to generate O2− during reverse flow in a dose-dependent fashion. These findings have important clinical implications for oxidative balance and NO bioavailability in regions of flow reversal in a normal and compromised cardiovascular system.