{"title":"Antioxidant potential of biflavonoid attenuates hyperglycemia by modulating the carbohydrate metabolic enzymes in high fat diet/streptozotocin induced diabetic rats.","authors":"Sundaram Ramalingam, Muthu Karuppiah, Muthusamy Thiruppathi, Shanthi Palanivelu, Sachdanandam Panchanatham","doi":"10.1080/13510002.2020.1722914","DOIUrl":"https://doi.org/10.1080/13510002.2020.1722914","url":null,"abstract":"<p><p><b>Objectives:</b> The present study was to isolate the biflavonoid (a bimolecular kaemferol structured molecule) and test its efficacy on oxidative stress and carbohydrate metabolic key enzymes in control and high fat diet and streptozotocin -induced diabetic rats.<b>Methods:</b> Type 2 diabetes was induced in male albino wistar rats by feeding them with high fat diet comprising of 84.3% standard laboratory chow, 5% lard, 10% yolk powder, cholesterol 0.2%, and 0.5% bile salt for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with low dose of streptozotocin (35 mg/kg, dissolved in 0.1 M sodium citrate buffer, pH 4.5).<b>Results:</b> At the end of the experimental period, diabetic control rats showed significant increase in plasma glucose, homeostatic model assessment of insulin resistance (HOMA-IR), glycosylated hemoglobin (HbA1c) with concomitant decrease in plasma insulin, total hemoglobin and body weight. The activities of key enzymes of carbohydrate metabolism, lipid peroxidation markers, antioxidant enzymes, glycogen content and glycogen synthase and glycogen phosphorylase were also altered in diabetic rats.<b>Discussion:</b> Oral administration of biflavonoid to diabetic rats significantly ameliorated all the biochemical alterations to near normal levels. The effect produced by the biflavonoid on various parameters was comparable to that of metformin.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"1-10"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1722914","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37605100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2020-12-01DOI: 10.1080/13510002.2020.1826750
Robert Gill, Sarah Mallay, Adrian Young, Ryan J Mailloux
{"title":"An investigation into the impact of deleting one copy of the <i>glutaredoxin-2</i> gene on diet-induced weight gain and the bioenergetics of muscle mitochondria in female mice fed a high fat diet.","authors":"Robert Gill, Sarah Mallay, Adrian Young, Ryan J Mailloux","doi":"10.1080/13510002.2020.1826750","DOIUrl":"https://doi.org/10.1080/13510002.2020.1826750","url":null,"abstract":"<p><p>Our group recently documented that male mice containing a deletion for one copy of the <i>glutaredoxin-2 (Grx2)</i> gene were completely protected from developing diet-induced obesity (DIO). <b>Objectives:</b> Here, we conducted a similar investigation but with female littermates. <b>Results:</b> In comparison to our recent publication using male mice, exposure of WT and GRX2+/- female mice to a HFD from 3-to-10 weeks of age did not induce any changes in body mass, circulating blood glucose, food intake, hepatic glycogen levels, or abdominal fat pad mass. Examination of the bioenergetics of muscle mitochondria revealed no changes in the rate of superoxide ( <math><msubsup><mi>O</mi> <mrow><mn>2</mn></mrow> <mrow><mo>∙</mo> <mo>-</mo></mrow> </msubsup> </math> )/hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) or O<sub>2</sub> consumption under different states of respiration or alterations in lipid peroxidation adduct levels regardless of mouse strain or diet. Additionally, we measured the bioenergetics of mitochondria isolated from liver tissue and found that partial loss of GRX2 augmented respiration but did not alter ROS production. <b>Discussion:</b> Overall, our findings demonstrate there are sex differences in the protection of female GRX2+/- mice from DIO, fat accretion, intrahepatic lipid accumulation, and the bioenergetics of mitochondria from muscle and liver tissue.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"87-94"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1826750","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38437167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2020-12-01DOI: 10.1080/13510002.2020.1752002
Katerina Hadrava Vanova, Michal Kraus, Jiri Neuzil, Jakub Rohlena
{"title":"Mitochondrial complex II and reactive oxygen species in disease and therapy.","authors":"Katerina Hadrava Vanova, Michal Kraus, Jiri Neuzil, Jakub Rohlena","doi":"10.1080/13510002.2020.1752002","DOIUrl":"https://doi.org/10.1080/13510002.2020.1752002","url":null,"abstract":"<p><p>Increasing evidence points to the respiratory Complex II (CII) as a source and modulator of reactive oxygen species (ROS). Both functional loss of CII as well as its pharmacological inhibition can lead to ROS generation in cells, with a relevant impact on the development of pathophysiological conditions, i.e. cancer and neurodegenerative diseases. While the basic framework of CII involvement in ROS production has been defined, the fine details still await clarification. It is important to resolve these aspects to fully understand the role of CII in pathology and to explore its therapeutic potential in cancer and other diseases.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"26-32"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1752002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37836301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2020-12-01DOI: 10.1080/13510002.2020.1731261
Shemani Vishalya Jagoda, Katie Marie Dixon
{"title":"Protective effects of 1,25 dihydroxyvitamin D<sub>3</sub> and its analogs on ultraviolet radiation-induced oxidative stress: a review.","authors":"Shemani Vishalya Jagoda, Katie Marie Dixon","doi":"10.1080/13510002.2020.1731261","DOIUrl":"https://doi.org/10.1080/13510002.2020.1731261","url":null,"abstract":"<p><p>The active vitamin D compound, 1,25-dihydroxyvitamin D3 (1,25D) is produced in skin cells following exposure to ultraviolet radiation (UV) from the sun. However, there are many harmful effects of UV which include DNA damage caused by direct absorption of UV, as well as that caused indirectly via UV-induced reactive oxygen species (ROS). Interestingly, 1,25D and analogs have been shown to reduce both direct and indirect UV-induced DNA damage in skin cells. This was accompanied by reductions in ROS and in nitric oxide products with 1,25D following UV. Moreover, following acute UV exposure, 1,25D has been demonstrated to increase p53 levels in skin, which would presumably allow for repair of cells with damaged DNA, or apoptosis of cells with irreparably damaged DNA. Previous studies have also shown that p53 reduces intracellular ROS. Furthermore, 1,25D has been shown to induce metallothioneins, which are potent free radical scavengers. In addition to these protective effects, 1,25D has been demonstrated to inhibit stress-activated c-Jun N-terminal kinases following UV exposure, and to increase levels of the stress-induced protein heme oxygenase-1 in a model of oxidative stress. Herein, we discuss the protective effects of 1,25D and analogs in the context of UV, oxidative stress and skin cancer.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"11-16"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1731261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37673799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2020-12-01DOI: 10.1080/13510002.2020.1739870
Yousra M El-Far, Ahmed E Khodir, Ahmad O Noor, Deina M Almasri, Alaa A Bagalagel, Reem M Diri, Hussam I Kutbi, Mohammed M H Al-Gayyar
{"title":"Selective cytotoxic activity and protective effects of sodium ascorbate against hepatocellular carcinoma through its effect on oxidative stress and apoptosis <i>in vivo</i> and <i>in vitro</i>.","authors":"Yousra M El-Far, Ahmed E Khodir, Ahmad O Noor, Deina M Almasri, Alaa A Bagalagel, Reem M Diri, Hussam I Kutbi, Mohammed M H Al-Gayyar","doi":"10.1080/13510002.2020.1739870","DOIUrl":"https://doi.org/10.1080/13510002.2020.1739870","url":null,"abstract":"<p><p><b>Objectives:</b> Hepatocellular carcinoma (HCC) is characterized by elevated in oxidative stress and inflammatory cytokines, which enhance destructive effects of the tumor. Therefore, we conducted this study to investigate the protective effects of sodium ascorbate against thioacetamide-induced HCC in rats through studying its effect on the apoptotic pathway in rats. In addition, <i>in vitro</i> activity of sodium ascorbate was investigated on HepG2 and compared with cisplatin.<b>Methods:</b> HCC was experimentally induced by injecting rats with 200 mg/kg thioacetamide intraperitoneally twice weekly for 16 weeks. Part of HCC rats was concomitantly treated with 100 mg/kg sodium ascorbate intraperitoneally during the 16-week period. Hepatic tissues were used for the determination of NFκB, Nrf2, TNF-α, caspase-3, caspase-8 and caspase-9.<b>Results:</b> Sodium ascorbate significantly attenuated HCC-induced reduction in the expression of NrF2 associated with a reduction in concentrations of hydrogen peroxide and superoxide anion. In addition, sodium ascorbate blocked HCC-induced increase in the expression of NFκB and TNF-α. Sodium ascorbate slightly increased the activity of caspase-3, -8 and -9 <i>in vitro</i> but inhibited their activities <i>in vivo</i>.<b>Conclusion:</b> In spite of the antioxidant and anti-inflammatory activity of sodium ascorbate, it produced selective cytotoxic activity via direct activation of the apoptotic pathway in cancer cells without affecting the apoptotic pathway in normal hepatic cells.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"17-25"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1739870","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37738819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"hnRNPK knockdown alleviates NLRP3 inflammasome priming by repressing FLIP expression in Raw264.7 macrophages.","authors":"Junxia Feng, Hongyan Li, Jingchun Li, Ping Meng, Lina Wang, Chunli Liu, Shili Zhao, Wei Sun, Yunfang Zhang","doi":"10.1080/13510002.2020.1857157","DOIUrl":"https://doi.org/10.1080/13510002.2020.1857157","url":null,"abstract":"<p><p><b>Objectives:</b> Inflammation is an important predisposing and progressive factor in chronic kidney disease (CKD). Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is associated with many fundamental cellular processes, but in chronic inflammatory pathologies remains unclear. <b>Methods:</b> An <i>in vitro</i> peripheral inflammation model was established using lipopolysaccharide (LPS)-stimulated mouse RAW264.7 macrophages, followed by inflammasome activation by ATP treatment. Knockdown of hnRNPK by sihnRNPK and FLICE-like inhibitory protein (FLIP) by siFLIP transfection were achieved in Raw264.7 macrophages. ELISA was used to determine the expression of IL-1β, IL-18 and TNF-α. Real time PCR was applied to detect the mRNA levels of hnRNPK, NOD-like receptors family pyrin domain-containing 3 (NLRP3), FLIP, Caspase-1, IL-1β and IL-18. Western blot and immunofluorescence were performed to detect relevant protein expressions. Co-immunoprecipitation (Co-IP) was used to assess the interaction of hnRNPK with FLIP. <b>Results:</b> Results showed that LPS plus ATP activated NLRP3 inflammasome, which evidenced by the up-regulation of TNF-α, IL-1β and IL-18. Notably, hnRNPK and FLIP were significantly up-regulated in activated NLRP3 inflammasome of macrophages. HnRNPK or FLIP knockdown significantly suppressed the activation of NLRP3 inflammasome, as reflected by down-regulation of Caspase-1, IL-1β and IL-18. Importantly, hnRNPK could directly bind to FLIP in activated NLRP3 inflammasome. <b>Discussion:</b> Our findings suggest that hnRNPK could promote the activation of NLRP3 inflammasome by directly binding FLIP, which might provide potential new therapeutic targets for CKD.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"104-111"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1857157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38679999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2020-12-01DOI: 10.1080/13510002.2020.1757877
Gabriela Nunes Marsiglio-Librais, Eloisa Aparecida Vilas-Boas, Christopher Carlein, Markus Daniel Alexander Hoffmann, Leticia Prates Roma, Angelo Rafael Carpinelli
{"title":"Evidence for NADPH oxidase activation by GPR40 in pancreatic β-cells.","authors":"Gabriela Nunes Marsiglio-Librais, Eloisa Aparecida Vilas-Boas, Christopher Carlein, Markus Daniel Alexander Hoffmann, Leticia Prates Roma, Angelo Rafael Carpinelli","doi":"10.1080/13510002.2020.1757877","DOIUrl":"https://doi.org/10.1080/13510002.2020.1757877","url":null,"abstract":"<p><p><b>Objective:</b> Investigate the involvement of the fatty acids receptor GPR40 in the assembly and activation of NADPH oxidase and the implications on pancreatic β-cell function.<b>Methods:</b> BRIN-BD11 β-cells were exposed to GPR40 agonist (GW9508) or linoleic acid in different glucose concentrations. Superoxide and H<sub>2</sub>O<sub>2</sub> were analyzed, respectively, by DHE fluorescence and by fluorescence of the H<sub>2</sub>O<sub>2</sub> sensor, roGFP2-Orp1. Protein contents of p47<sup>phox</sup> in plasma membrane and cytosol were analyzed by western blot. NADPH oxidase role was evaluated by p22<sup>phox</sup> siRNA or by pharmacological inhibition with VAS2870. NOX2 KO islets were used to measure total cytosolic calcium and insulin secretion.<b>Results:</b> GW9508 and linoleic acid increased superoxide and H<sub>2</sub>O<sub>2</sub> contents at 5.6 and 8.3 mM of glucose. In addition, in 5.6 mM, but not at 16.7 mM of glucose, activation of GPR40 led to the translocation of p47<sup>phox</sup> to the plasma membrane. Knockdown of p22<sup>phox</sup> abolished the increase in superoxide after GW9508 and linoleic acid. No differences in insulin secretion were found between wild type and NOX2 KO islets treated with GW9508 or linoleic acid.<b>Discussion:</b> We report for the first time that acute activation of GPR40 leads to NADPH oxidase activation in pancreatic β-cells, without impact on insulin secretion.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"41-50"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1757877","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37889503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2020-12-01DOI: 10.1080/13510002.2020.1795587
Alistair R Mallard, Siri Marte Hollekim-Strand, Charlotte Björk Ingul, Jeff S Coombes
{"title":"High day-to-day and diurnal variability of oxidative stress and inflammation biomarkers in people with type 2 diabetes mellitus and healthy individuals.","authors":"Alistair R Mallard, Siri Marte Hollekim-Strand, Charlotte Björk Ingul, Jeff S Coombes","doi":"10.1080/13510002.2020.1795587","DOIUrl":"https://doi.org/10.1080/13510002.2020.1795587","url":null,"abstract":"<p><p><b>Objective:</b> Assess the variability and differences in oxidative stress, antioxidant, and inflammatory biomarkers in people with type 2 diabetes mellitus (T2D) and healthy controls. <b>Methods::</b> Ten men and women diagnosed with T2D and ten healthy matched controls (CON) were recruited. Participants had venous blood taken at six different time points on different days, three in the morning (after overnight fast) and three in the afternoon. Inflammation (IL-6, 8, 10 and TNF-α), oxidative stress/antioxidant biomarkers (F<sub>2</sub>-isoprostanes, protein carbonyls, total antioxidant capacity (TAC), glutathione peroxidase activity, IL-6, 8 & 10 and TNF-α) were assessed. <b>Results::</b> Biomarker concentrations were similar between groups. There was large variability in nearly all biomarkers for both groups. For inflammatory measures, intra-individual coefficients of variation (CV) ranged from 64.0-92.1% and 100.9-259.0% for inter-individual differences. CVs for oxidative stress markers were lower (7.4-31.2% for intra-individual and 8.6-43.0% for inter-individual). TAC had the lowest intra-individual CV - 7% for T2D and 8% for CON. Protein carbonyls were more variable in the afternoon (34% CV) compared to morning (24% CV) in CON. IL-6 intra-individual CV was different between groups for afternoon measurements (93% T2D, 60% CON). <b>Conclusion::</b> Oxidative stress and inflammatory biomarkers show considerable variation in both T2D and healthy populations. <b>Trial registration:</b> ClinicalTrials.gov identifier: NCT01206725.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"64-69"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1795587","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38185010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2020-12-01DOI: 10.1080/13510002.2020.1804711
Patience N Ogbu, Evelyn O Ugota, Rita U Onwuka, Ikechukwu M Ogbu, Chinyere Aloke
{"title":"Effect of acetogenin fraction of <i>Annona muricata</i> leaves on antioxidant status and some indices of benign prostatic hyperplasia in rats.","authors":"Patience N Ogbu, Evelyn O Ugota, Rita U Onwuka, Ikechukwu M Ogbu, Chinyere Aloke","doi":"10.1080/13510002.2020.1804711","DOIUrl":"https://doi.org/10.1080/13510002.2020.1804711","url":null,"abstract":"<p><p><b>ABSTRACT</b> <b>Objectives:</b> This work investigated the effect of acetogenin-rich fraction of <i>Annona muricata</i> leaves (AFAL) on antioxidant status and some markers of benign prostatic hyperplasia (BPH) in rats. <b>Methods:</b> BPH was experimentally induced in the rats by subcutaneous injection of testosterone propionate (TP, 3 mg/kg) for 28 consecutive days. The rats were administered orally different doses of AFAL (100 and 200 mg/kg) for 7 days. Prostate-specific antigen (PSA), prostate weight, relative prostate weight, prostate protein content and oxidative stress indices of the rats were evaluated. <b>Results:</b> It was observed that 200 mg/kg AFAL significantly reduced the PSA level, mean prostate weights and mean relative prostate weights of the test rats compared to the TP group, and the values were not significantly different from the normal control and group treated with a standard drug. The plant extract also significantly enhanced the antioxidant capacity of the test rats which were evidently compromised in the group that received the exogenous hormone alone. Histopathology of the prostate showed a marked recovery for the test rats after treatment with AFAL. <b>Conclusion:</b> Oral administration of acetogenin-rich fraction of <i>Annona muricata</i> leaves ameliorated TP-induced BPH in rats and significantly enhanced the antioxidant capacity of the rats.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"80-86"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1804711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38337999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Redox ReportPub Date : 2020-12-01DOI: 10.1080/13510002.2020.1787662
Keiko Murakami, Masataka Yoshino
{"title":"Generation of reactive oxygen species by hydroxypyridone compound/iron complexes.","authors":"Keiko Murakami, Masataka Yoshino","doi":"10.1080/13510002.2020.1787662","DOIUrl":"https://doi.org/10.1080/13510002.2020.1787662","url":null,"abstract":"<p><p><b>Objectives:</b> Prooxidant properties of iron-binding hydroxypyridone compounds including deferiprone and mimosine were analyzed. <b>Methods:</b> Hydroxypyridone/iron-dependent production of reactive oxygen species was evidenced by the inactivation of aconitase, the most sensitive enzyme to oxidative stress in permeabilized yeast cells. <b>Results and Discussion:</b> Deferiprone and mimosine produced reactive oxygen species in the presence of ferrous sulfate. The inactivation required sodium azide the inhibitor of catalase, and addition of TEMPOL, a scavenger of superoxide radical, protected aconitase from the inactivation, suggesting that the superoxide radical produced from the hydroxypyridone/iron complex is responsible for the inactivation of aconitase. A principal role of superoxide radical was further supported by the finding that the hydroxypyridone/iron complex can inactivate aconitase in the presence of cyanide the inhibitor of superoxide dismutase. Deferiprone and mimosine stimulated the Fe<sup>2+</sup> oxidation, resulting in the one-electron reduction of oxygen to form superoxide anion, which can inactivate aconitase by oxidizing the prosthetic iron-sulfur cluster. Mimosine further stimulated the ascorbate/iron-dependent formation of 8-hydroxy-2'-deoxyguanosine in DNA. <b>Conclusion:</b> Biological toxicity of mimosine and deferiprone reported previously can be accounted for by the prooxidant properties of hydroxypyridone compounds: coordination complex with iron generates reactive oxygen species resulting in the disturbance of mitochondrial energy metabolism and DNA damage.</p>","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"25 1","pages":"59-63"},"PeriodicalIF":3.8,"publicationDate":"2020-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1080/13510002.2020.1787662","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38110571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}