Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe最新文献

{"title":"Recirculating bioavailable nicotine metabolite using ascorbic acid: A pragmatic approach for treating nicotine dependence","authors":"Murugesan Arumugam ,&nbsp;Raman Lakshmi Sundaram ,&nbsp;Vishal Jayajothi ,&nbsp;Manish Arul ,&nbsp;Jerad A Suresh ,&nbsp;Sathesh Kumar Kesavan","doi":"10.1016/j.arres.2023.100089","DOIUrl":"https://doi.org/10.1016/j.arres.2023.100089","url":null,"abstract":"<div><p>Nicotine undergoes metabolism, converting into the oxidized metabolite cotinine, which can persist in the body for several weeks and potentially lead to fatal conditions, such as cancer. Conventional nicotine replacement therapy provides additional nicotine to the body, thereby increasing the chance of accumulating the toxic metabolite cotinine. Consequently, we proposed a hypothesis: converting cotinine back into nicotine using a suitable reducing agent, such as ascorbic acid, could be a practical approach. This conversion would allow cotinine to be reutilized for its central nervous system effects before its eventual elimination from the body. In the current study, we examined this hypothesis by using plasma samples from smokers. Volunteers (both non-smokers and smokers) were screened and recruited for this study. In the initial time- and dose-dependent studies, we incubated plasma samples from non-smokers with cotinine and ascorbic acid. Changes in cotinine and nicotine levels were quantified using HPLC-PDA. Based on the findings of these experiments, we selected a concentration of 1 µM ascorbic acid and incubated it with plasma samples from 25 smokers for 10 min. A time-dependent study revealed that nicotine was detected in non-smokers' plasma samples after a 10-minute incubation with 28.38 µM of both cotinine and ascorbic acid. In a subsequent dose-dependent study, the maximum concentration of nicotine was observed at 1 µM ascorbic acid. Among the 25 samples of smokers’ plasma, the mean nicotine concentration increased from 0.565 ± 0.196 to 1.937 ± 0.622 µM (<em>P</em> = 0.0081), while cotinine levels decreased from 1.278 ± 0.253 to 0.754 ± 0.137 µM (<em>P</em> = 0.0087). This study conclusively demonstrated that ascorbic acid, at a specified concentration, effectively converts cotinine back into nicotine in smokers' plasma. Importantly, this conversion did not occur in water or in the absence of ascorbic acid in the plasma, indicating enzyme involvement.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"10 ","pages":"Article 100089"},"PeriodicalIF":0.0,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667137923000292/pdfft?md5=8cd5c7ca0e9e1be41972c27b4d8ccf6e&pid=1-s2.0-S2667137923000292-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138490208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of acetyl-11-keto-beta boswellic acid on hepatic membrane dynamics and lipidiome during conditions of benzo(a)pyrene induced toxicity","authors":"Rishav Puri ,&nbsp;Priti Bhardwaj ,&nbsp;Sunil Kumar Dhatwalia,&nbsp;Devinder Kumar Dhawan","doi":"10.1016/j.arres.2023.100086","DOIUrl":"https://doi.org/10.1016/j.arres.2023.100086","url":null,"abstract":"<div><h3>Background and Aim</h3><p>Pollution and lifestyle changes expose mankind to a number of toxicants such as polycyclic aromatic hydrocarbons that may cause life-threatening diseases. The present study was undertaken to explicate the protective role of Acetyl-11-Keto-Beta Boswellic Acid (AKBA), if any, in containing benzo(a)pyrene (BaP) induced alterations on hepatic membrane dynamics and lipidiome in female rats.</p></div><div><h3>Experimental procedure</h3><p>The animals were divided into five groups viz. Normal control, Vehicle treated, BaP treated, AKBA treated and BaP + AKBA treated. To induce hepatotoxicity, BaP was administered orally at a dose level of 50 mg/kg b.wt. dissolved in olive oil twice a week for 4 weeks. AKBA was supplemented to animals four weeks prior to BaP treatment and continued for 8 weeks at a dose level of 50 mg/kg b.wt. thrice a week. Certain key indices that included oxidative stress biomarkers, lipid profile of membranes, membrane fluidity parameters and activities of ATPases were studied.</p></div><div><h3>Results and Conclusion</h3><p>The results showed that benzo(a)pyrene treatment resulted in a significant increase in the levels of lipid peroxidation (LPO) and ROS but caused a significant decrease in the levels of total lipids, phospholipids, cholesterol, glycolipids and activities of ATPases. Hepatic membrane fluidity as assessed by 1,6-Diphenyl-1,3,5-hexatriene (DPH) and Pyrene fluorescence probes was significantly increased in rats intoxicated with BaP. Interestingly, AKBA supplementation to BaP treated rats appreciably contained altered membrane dynamics and lipidiome as well as modulated hepatotoxicity by skirmishing activities of oxidative stress markers and also improved hepatic histoarchitecture. Our study thus concludes that AKBA can be used as a prophylactic intervention in providing protection to hepatocytes as it maintains membrane integrity in conditions of BaP induced toxicity.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100086"},"PeriodicalIF":0.0,"publicationDate":"2023-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667137923000267/pdfft?md5=753298c33766b5e29f7d10b6cf9f195f&pid=1-s2.0-S2667137923000267-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92019991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGCG: The antioxidant powerhouse in lung cancer management and chemotherapy enhancement","authors":"Amit Sehgal ,&nbsp;Majaz Ahmad Bhat ,&nbsp;Deeksha Dogra ,&nbsp;Suman Rawat ,&nbsp;Sunil Kumar Dhatwalia","doi":"10.1016/j.arres.2023.100085","DOIUrl":"https://doi.org/10.1016/j.arres.2023.100085","url":null,"abstract":"<div><p>Lung cancer is the main cause of cancer-related deaths throughout the world. Its treatment involves intensive cycles of chemotherapy and radiotherapy, which are associated with serious adverse effects. EGCG, an active component of green tea/white tea, regulates cell molecular pathways of apoptosis, angiogenesis, proliferation, differentiation, and self-renewal ability of cancer stem cells. It also acts as a pro-oxidant that can cause cell death in cancer cells via apoptosis. It can control lung carcinogenesis by altering the molecules involved in multiple signal transduction pathways like Ras-GTPase, ERK, COX2, VEGF, and protein kinases. Moreover, it can also affect other signalling molecules or pathways such as DNMT1, MAPK, NF-κB, Bcl/Bax, HIF-1α, EGFR, Akt/PI3, Wnt/β-catenin, caspases, NEAT1, TGF-β, HDGF, and CLOCK. Recent studies on cell lines and animals have focused on the role of EGCG in enhancing the efficacy of chemotherapeutic drugs and reducing their adverse effects. The low bioavailability and rapid metabolism of EGCG can act as a hurdle in the translation of this agent from lab to bedside. The uses of synthetic agents such as COMT inhibitors and nano-drug delivery tools have been shown to enhance the plasma levels of EGCG and its cancer preventive and therapeutic ability.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100085"},"PeriodicalIF":0.0,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667137923000255/pdfft?md5=716f139a1f09137a3cdd5ec838398cb3&pid=1-s2.0-S2667137923000255-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92019990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Betaine Intervention as a Novel Approach to Preventing Doxorubicin-Induced Cardiotoxicity","authors":"Aiswarya Jaiswal ,&nbsp;Pushkar Singh Rawat ,&nbsp;Sumeet Kumar Singh ,&nbsp;Jasvinder Singh Bhatti ,&nbsp;Amit Khurana ,&nbsp;Umashanker Navik","doi":"10.1016/j.arres.2023.100084","DOIUrl":"https://doi.org/10.1016/j.arres.2023.100084","url":null,"abstract":"<div><p>The anthracycline anticancer drug doxorubicin (Dox) is widely prescribed for treating lung, ovary, breast, lymphoma, sarcoma, and pediatric cancer. Mechanistically, Dox intercalates the DNA and inhibits the topoisomerase II enzyme in fast-proliferating cancer. The clinical application of Dox is limited due to its cardiotoxicity, including congestive heart failure, alterations in myocardial structure, arrhythmia, and left ventricular dysfunction. Dox causes cardiotoxicity via various mechanisms, including oxidative stress, mitochondrial dysfunctioning, deranged Ca²⁺ homeostasis, inflammation, fibrosis, downregulating AMPK, etc. Betaine is a zwitterion-based drug known as N, N, N trimethylglycine that regulates the methionine cycle and homocysteine (a risk factor for cardiovascular disease) detoxification through betaine-homocysteine methyltransferases. Betaine is nontoxic and has several beneficial effects in different disease models. Betaine treatment decreases the amyloid β generation, reduces obesity, improves steatosis and fibrosis, and activates AMP-activated protein kinase (AMPK). Further, betaine downregulates 8‑hydroxy-2-deoxyguanosine, malondialdehyde, and upregulates catalases, glutathione peroxidase, and superoxide dismutase activity. Therefore, we hypothesized that betaine might be a rational drug candidate to effectively combat Dox-associated oxidative stress, inflammation, and mitochondrial dysfunction.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100084"},"PeriodicalIF":0.0,"publicationDate":"2023-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49776019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxiredoxin-1 is an H2O2 safe-guard antioxidant and signalling enzyme in M1 macrophages","authors":"Daria Ezeriņa ,&nbsp;Trung Nghia Vo ,&nbsp;Ting Luo ,&nbsp;Yvon Elkrim ,&nbsp;Anna Escoda Suarez ,&nbsp;Gaëtan Herinckx ,&nbsp;Didier Vertommen ,&nbsp;Damya Laoui ,&nbsp;Jo A. Van Ginderachter ,&nbsp;Joris Messens","doi":"10.1016/j.arres.2023.100083","DOIUrl":"https://doi.org/10.1016/j.arres.2023.100083","url":null,"abstract":"<div><p>Macrophages are characterised by their high plasticity and ability to adapt their phenotype and functionality in response to environmental cues, resulting in a spectrum of activation states the two extremes of which are M1 and M2. Reactive oxygen species, such as hydrogen peroxide, are among the cues that impact macrophage polarisation. Moreover, high levels of hydrogen peroxide play a role in the phagocytic response executed by M1 macrophages. Therefore, macrophages must balance the need to shield themselves from the harmful effects of hydrogen peroxide bursts with the ability to interpret hydrogen peroxide signals from the surroundings and initiate a cellular response. Peroxiredoxins (PRDX) are proteins capable of performing both roles. Specifically, PRDX1 and PRDX5 have been demonstrated to safeguard macrophages against reactive oxygen species while also impacting their polarisation status. Previously conducted studies did not differentiate between the polarisation state of macrophages or investigate the signalling events triggered by PRDXs. In this study, we utilised bone marrow-derived murine macrophages polarised to the M1 and M2 states. Our findings revealed that the expression of PRDX1 was significantly higher in M1 macrophages than in M2 and unpolarised macrophages. Moreover, we present evidence that in M1 macrophages, PRDX1 interacts with ASK1, its established interaction partner, and also binds to other proteins that regulate the cellular antioxidant response. Interestingly, we found that pharmacological elevation of hydrogen peroxide levels leads to an increase in PRDX1 expression on the mRNA level, but not in the highly related PRDX2 expression. Taken together, our findings suggest that PRDX1 plays a critical role in macrophage antioxidant defence and redox signalling, and provide scope for exploring redox-signalling proteins as highly sought-after candidates for macrophage repolarisation.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100083"},"PeriodicalIF":0.0,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49776021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Terpinen-4-ol, A volatile terpene molecule, extensively electrifies the biological systems against the oxidative stress-linked pathogenesis","authors":"Jobaier Ibne Deen ,&nbsp;A.N.M. Shahriar Zawad ,&nbsp;Mijbah Uddin ,&nbsp;Muhammad Abid Hasan Chowdhury ,&nbsp;Salahuddin Qader Al Araby ,&nbsp;Md. Atiar Rahman","doi":"10.1016/j.arres.2023.100082","DOIUrl":"https://doi.org/10.1016/j.arres.2023.100082","url":null,"abstract":"<div><p>Terpenes and their derivatives in essential oil have been raising an upstream interest due to their unwavering health-promoting effects and safety profiles, although the individual essential oil components are inadequately assessed for their biological potential. Terpinen-4-ol, a bioactive natural terpene-derivative unambiguously distributed in most essential oil sources, is displaying a very remarkable role as a phytometabolite. This review, therefore, deciphered the health-promoting effects of Terpinen-4-ol in oxidative stress-linked diseases including neurodegenerative disorders, cancers, cardiovascular diseases, diabetes, and inflammatory disorders. Using Google as a search engine, this systematic review unraveled 217 relevant articles out of 857 search results from Web of Science, PubMed, and ScienceDirect. Terpinen-4-ol is reported to increase superoxide dismutase, decrease glutathione-S-transferase and acetylcholine esterase, inhibit NF-κB and NLRP3 inflammasome activation pathway, downregulate the α-amylase activity and increase insulin sensitivity, and substantially inhibit the generation of inflammatory mediators such as IL-1β, IL-6, IL-10. Despite several beneficial actions of Terpinen-4-ol, it has hardly been expedited to use as pharmaceutical therapeutic target for unveiled biological activities. In that context, this review has focused on the role of Terpinen-4-ol in attenuating oxidative stress and stress-linked pathophysiological conditions unraveling a research gap on it to manifest its best pharmaceutical and therapeutic uses.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100082"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49776020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of metabolism, stress response, and sod1 activity by cytosolic thioredoxins in yeast depends on growth phase","authors":"Cecilia Picazo ,&nbsp;C. Alicia Padilla ,&nbsp;Brian McDonagh ,&nbsp;Emilia Matallana ,&nbsp;José A. Bárcena ,&nbsp;Agustín Aranda","doi":"10.1016/j.arres.2023.100081","DOIUrl":"https://doi.org/10.1016/j.arres.2023.100081","url":null,"abstract":"<div><p>Reactive Oxygen Species (ROS) can be harmful compounds that can cause damage to macromolecules like lipids, proteins, and DNA when their levels exceed cellular defense mechanisms. Cells have protection and ROS detoxification systems, including thioredoxin and glutaredoxin systems, to counteract oxidative stress. The role of cytosolic thioredoxin system (cTRX) was investigated in different growth phases using a mutant strain lacking both <em>TRX1</em> and <em>TRX2</em>. The mutant showed a defect in survival during the non-dividing state or stationary phase. The levels of glutathione, an antioxidant, in the mutants were higher in both total and reduced glutathione, indicating an increase in oxidative response. The mutant also showed an increase in protein-bound glutathione, suggesting a compensatory mechanism to counter balance oxidative stress. Proteomic analysis revealed changes in the expression of various proteins in the absence of cytosolic thioredoxins. Upregulated proteins in both exponential and stationary phases were mainly related to oxidative stress response and metabolism. Downregulated proteins in both phases were associated with glycerol metabolism, glycolysis, and ATP synthesis. These changes indicated a compensatory response to redox imbalance caused by the absence of cytosolic thioredoxins. Further analysis focused on the reversible oxidation of cysteine residues in proteins. Several proteins were identified with cysteines susceptible to reversible oxidation, and their oxidation status was affected by the absence of cytosolic thioredoxins. Notably, cysteine 146 of cytosolic Superoxide Dismutase 1 (Sod1) was more oxidized in growth phase, while oxidation of ribosomal proteins was seen only in exponential phase.</p><p>Overall, this study provides insights into the role of cytosolic thioredoxin system in growth, aging, in maintaining redox balance, protecting against oxidative stress as well as its impact on <em>SOD1</em> activity and glutathionylation.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100081"},"PeriodicalIF":0.0,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49776022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOX1 and PRDX6 synergistically support migration and invasiveness of hepatocellular carcinoma cells through enhanced NADPH oxidase activity","authors":"Daniel J. Lagal ,&nbsp;J. Antonio Bárcena ,&nbsp;Raquel Requejo-Aguilar ,&nbsp;C. Alicia Padilla ,&nbsp;Thomas L. Leto","doi":"10.1016/j.arres.2023.100080","DOIUrl":"10.1016/j.arres.2023.100080","url":null,"abstract":"<div><p>The NADPH oxidase 1 (NOX1) complex formed by proteins NOX1, p22phox, NOXO1, NOXA1, and RAC1 plays an important role in the generation of superoxide and other reactive oxygen species (ROS) which are involved in normal and pathological cell functions due to their effects on diverse cell signaling pathways. Cell migration and invasiveness are at the origin of tumor metastasis during cancer progression which involves a process of cellular de-differentiation known as the epithelial-mesenchymal transition (EMT). During EMT cells lose their polarized epithelial phenotype and express mesenchymal marker proteins that enable cytoskeletal rearrangements promoting cell migration, expression and activation of matrix metalloproteinases (MMPs), tissue remodeling, and cell invasion during metastasis. In this work, we explored the importance of the peroxiredoxin 6 (PRDX6)-NOX1 enzyme interaction leading to NOXA1 protein stabilization and increased levels of superoxide produced by NOX in hepatocarcinoma cells. This increase was accompanied by higher levels of N-cadherin and MMP2, correlating with a greater capacity for cell migration and invasiveness of SNU475 hepatocarcinoma cells. The increase in superoxide and the associated downstream effects on cancer progression were suppressed when phospholipase A₂ or peroxidase activities of PRDX6 were abolished by site-directed mutagenesis, reinforcing the importance of these catalytic activities in supporting NOX1-based superoxide generation. Overall, these results demonstrate a clear functional cooperation between NOX1 and PRDX6 catalytic activities which generate higher levels of ROS production, resulting in a more aggressive tumor phenotype.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100080"},"PeriodicalIF":0.0,"publicationDate":"2023-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45901091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascorbate mediates the non-enzymatic reduction of nitrite to nitric oxide","authors":"Juan Du ,&nbsp;Milos R. Filipović ,&nbsp;Brett A. Wagner ,&nbsp;Garry R. Buettner","doi":"10.1016/j.arres.2023.100079","DOIUrl":"10.1016/j.arres.2023.100079","url":null,"abstract":"<div><p>Nitric oxide (NO^•) generated by nitric oxide synthases is involved in many physiological and pathophysiological processes. However, non-enzymatic formation of NO^• also occurs <em>in vivo</em>. Here we investigated the production of NO^• from nitrite, as facilitated by ascorbate, over the pH range of 2.4–7.4. Using a nitric oxide electrode, we observed at low pH a rapid generation of NO^• from nitrite and ascorbate that slows with increasing pH. The formation of NO^• was confirmed by its reaction with oxyhemoglobin. In the ascorbate/nitrite system a steady-state level of NO^• was achieved, suggesting that a futile redox cycle of nitrite-reduction by ascorbate and NO^•-oxidation by dioxygen was established. However, at pH-values of around 7 and greater, the direct reduction of nitrite by ascorbate is very slow; thus, this route to the non-enzymatic production of NO^• is not likely to be significant process <em>in vivo</em> in environments having a pH around 7.4. The production of nitric oxide by nitrite and ascorbate would be important only in areas of lower pH, <em>e.g.</em> stomach/digestive system, sites of inflammation, and areas of hypoxia such as tumor tissue. In patients receiving very large doses of ascorbate delivered by intravenous infusion, plasma levels of ascorbate on the order of 20 - 30 mM can be achieved. After infusion, levels of nitrate and nitrite in plasma were unchanged. Thus, in blood and tissue that maintain a pH of about 7.4, the reduction of nitrite to nitric oxide by ascorbate appears to be insignificant, even at very large, pharmacological levels of ascorbate.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100079"},"PeriodicalIF":0.0,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10486277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10605702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of dichlorvos on kidney functions with reference to altered AChE gene expression in mice","authors":"Sonam Agarwal ,&nbsp;Renu Bist ,&nbsp;Himani Kuntal ,&nbsp;D.K. Bhatt","doi":"10.1016/j.arres.2023.100078","DOIUrl":"10.1016/j.arres.2023.100078","url":null,"abstract":"<div><h3>Background</h3><p>The dichlorvos is reported to cause toxic effects by inducing oxidative stress via modification in antioxidant enzymes. Besides, the neurotransmitters (NTs) linked enzyme acetylcholinesterase (AChE) is also inhibited in the kidneys of dichlorvos treated mice. The exact mechanism of toxic action of dichlorvos on AChE gene expression is not clearly understood.</p></div><div><h3>Purpose</h3><p>The present study is aimed to elucidate a possible mechanism by which dichlorvos induces nephrotoxicity in mice. Moreover, it is further clarified that how AChE gene expression gets modified in dichlorvos treated mice.</p></div><div><h3>Study design and methods</h3><p>The study was carried out on healthy male mice, 4–5 weeks old weighing 21±1 g. The animals were equally divided into two groups. The first group served as control, whereas the animals of the second group were given dichlorvos 40 mg/kg b.w. i.p. for 21 days.</p></div><div><h3>Results</h3><p>The treatment of dichlorvos revealed decline in various antioxidants such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GP_X), glutathione-S-transferase (GST) and reduced glutathione (GSH) in mice kidneys. The significance level of these antioxidants ranged from <em>P</em>&lt; 0.05 to <em>P</em>&lt;0.001.</p></div><div><h3>Conclusion</h3><p>The dichlorvos is causing increase in production of highly reactive oxygen species (ROS) owing to inhibition of antioxidant enzymes studied in the present study. The ROS being highly reactive molecules AChE gene seems to be mutated. This is reflected in the modulation of kidney functions by increasing levels of urea, uric acid and creatinine.</p></div>","PeriodicalId":72106,"journal":{"name":"Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe","volume":"9 ","pages":"Article 100078"},"PeriodicalIF":0.0,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41796313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}