Wen Qi, Smitha U Nair, David I Pattison, Robert F Anderson
{"title":"Redox factors in the antioxidant activity of nitroxides toward DNA guanyl and 2-deoxyribose-peroxyl radicals.","authors":"Wen Qi, Smitha U Nair, David I Pattison, Robert F Anderson","doi":"10.1080/10715762.2024.2417278","DOIUrl":"https://doi.org/10.1080/10715762.2024.2417278","url":null,"abstract":"<p><p>A series of eight nitroxide compounds (four substituted piperidines, three pyrrolidines and one oxo-piperidine) are found to undergo electron transfer to 2'-deoxyribose-peroxyl and the guanyl radical. One-electron oxidation potentials of the nitroxides to oxoammonium cations (oxoammonium reduction potential), <i>E</i><sup>0'</sup>, have been measured against a common redox indicator, chlorpromazine, and found to span the range 751 ± 15 mV to 973 ± 15 mV. Fast chemical reduction of the 2'-deoxyribose-peroxyl radical to the hydroperoxide, generated by <b><sup>•</sup></b>OH radical attack on 2-deoxyribose, dR, in oxygenated aqueous solution, is a redox-dependent reaction, with rate constants of 0.8-3.5 x 10<sup>7</sup> M<sup>-1</sup> s<sup>-1</sup>.The guanyl radicals, produced upon one-electron oxidation of 2'-deoxyguanosine monophosphate, dG, by the selenite radical, SeO<sub>3</sub><b><sup>•</sup></b><sup>-</sup>, react with the nitroxides in a redox-independent reaction with diffusion rate constants of 1-2 x 10<sup>8</sup> M<sup>-1</sup> s<sup>-1</sup>. These findings represent a possible antioxidant role for nitroxides in the fast chemical repair of DNA radicals, which is supported by an <i>in vitro</i> strand break study using a plasmid.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-9"},"PeriodicalIF":3.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paweł Sutkowy, Jarosław Paprocki, Jacek Piechocki, Alina Woźniak
{"title":"The impact of hyperbaric oxygen therapy on the redox balance of patients with diabetic foot syndrome.","authors":"Paweł Sutkowy, Jarosław Paprocki, Jacek Piechocki, Alina Woźniak","doi":"10.1080/10715762.2024.2417286","DOIUrl":"https://doi.org/10.1080/10715762.2024.2417286","url":null,"abstract":"<p><p>Diabetic foot wounds associated with oxidative stress are treated with hyperbaric oxygen (HBO), but that may also induce the stress itself; therefore, we studied the effect of HBO treatments on the oxidant-antioxidant balance in the venous blood of patients with diabetic foot syndrome. In addition, blood counts were also examined. 14 male patients (24-74 years), at risk of lower limb amputation were treated with 30 HBO procedures (60 min of the inhalation of pure oxygen at a pressure of 2.5 atm per day, 5 days a week). The control group consisted of 29 healthy male volunteers aged 25-69 years. No members of the group had been subjected to HBO therapy previously (ClinicalTrials.gov, no. NCT06401941). The analyzed redox parameters did not change during the experiment in the patients (<i>p</i> > 0.05). The concentration of thiobarbituric acid reactive substances (TBARS) in the plasma was higher in the patients before the first and after the thirtieth HBO treatments when compared to the control group. In contrast, the TBARS concentration in erythrocytes was lower in the patients after the first treatment vs. the controls. Moreover, the higher activity of catalase in the patients' erythrocytes was noted before the therapy and after the first and last treatments compared to the controls. HBO therapy increased the percentage of monocytes and platelet volume, but it decreased the volume of platelets in the patients' blood. HBO therapy does not affect the oxidant-antioxidant balance disturbed in diabetic foot patients.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-10"},"PeriodicalIF":3.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiyu Li, Chao Cui, Liang Xu, Mingfeng Ding, Yinghui Wang
{"title":"Metformin suppresses metabolic dysfunction-associated fatty liver disease by ferroptosis and apoptosis via activation of oxidative stress.","authors":"Zhiyu Li, Chao Cui, Liang Xu, Mingfeng Ding, Yinghui Wang","doi":"10.1080/10715762.2024.2417279","DOIUrl":"https://doi.org/10.1080/10715762.2024.2417279","url":null,"abstract":"<p><p>Metformin is known for its antioxidant properties and ability to ameliorate metabolic dysfunction-associated fatty liver disease (MAFLD) and is the focus of this study. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is linked to MAFLD risk. This study investigated the effects of metformin on ferroptosis in free fatty acid (FFA)-treated Huh7 hepatoma cells and its association with MAFLD risk. Using Western blot, immunofluorescence, and ELISA, this study revealed that FFA treatment led to increased intracellular fat and iron accumulation, heightened Lp-PLA2 expression, reduced levels of the cysteine transporter SLC7A11 and glutathione peroxidase 4 (GPX4), altered glutathione (GSH)/oxidized glutathione (GSSG) ratios, generation of reactive oxygen species (ROS), and initiation of lipid peroxidation, which ultimately resulted in cell ferroptosis. Importantly, metformin reversed FFA-induced iron accumulation, and this effect was attenuated by ferrostatin-1 but enhanced by erastin, RSL3, and si-GPX4. Additionally, metformin activated antioxidant and antiapoptotic mechanisms, which reduced lipid peroxidation and suppressed Lp-PLA2 expression in FFA-treated Huh7 cells. In conclusion, our findings indicate that metformin may protect against MAFLD by inhibiting iron accumulation and Lp-PLA2 expression through the ROS, ferroptosis, and apoptosis signaling pathways. This study highlights potential therapeutic strategies for managing MAFLD-related risks and emphasizes the diverse roles of metformin in maintaining hepatocyte balance.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-16"},"PeriodicalIF":3.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-10-01Epub Date: 2024-11-06DOI: 10.1080/10715762.2024.2421174
Hideki Mori, Hidekazu Suzuki
{"title":"Cutting-edge insights into <i>Helicobacter</i> research.","authors":"Hideki Mori, Hidekazu Suzuki","doi":"10.1080/10715762.2024.2421174","DOIUrl":"10.1080/10715762.2024.2421174","url":null,"abstract":"<p><p>Non-<i>Helicobacter pylori</i> Helicobacter (NHPH) species are emerging as significant gastric pathogens. Despite their clinical importance, NHPH infections are less studied compared to <i>Helicobacter pylori</i> (<i>H. pylori</i>) due to their lower prevalence and diagnostic challenges. Zoonotic transmission, particularly from pigs, dogs, and cats, underscores the need for improved diagnostic methods and heightened clinical awareness. Gastric cancer (GC) remains a major global health issue, with <i>H. pylori</i> being a primary risk factor. The eradication of <i>H. pylori</i> reduces GC risk, but post-eradication surveillance is essential. Endoscopic findings, especially those from the Kyoto classification, and noninvasive biomarkers play crucial roles in early GC detection and risk assessment. The increasing antibiotic resistance in <i>H. pylori</i> necessitates new treatment strategies. Novel therapies, such as vonoprazan-based regimens, and alternatives like sitafloxacin and rifabutin, are being developed to improve eradication success rates. Understanding the fundamental mechanisms of gastric carcinogenesis, including the roles of oxidative stress and cancer stem cells, is key to advancing treatment. Targeting specific molecular pathways offers potential for more effective therapies.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"641-647"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-10-01Epub Date: 2024-06-22DOI: 10.1080/10715762.2024.2360013
Tanushree Das, Sanchaita Mondal, Sujata Das, Sanjib Das, Krishna Das Saha
{"title":"Enhanced anticancer activity of (-)-epigallocatechin-3-gallate (EGCG) encapsulated NPs toward colon cancer cell lines.","authors":"Tanushree Das, Sanchaita Mondal, Sujata Das, Sanjib Das, Krishna Das Saha","doi":"10.1080/10715762.2024.2360013","DOIUrl":"10.1080/10715762.2024.2360013","url":null,"abstract":"<p><p>(-)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol of green tea, has chemo-preventive effects against various cancer cells. Nanoparticles (NPs) carrying different ligands are able to specifically interact with their receptors on different cancer cells that can provide effective release of cytotoxic drugs. In the present study, we have prepared EGCG entrapped NPs using PLGA (poly(d,l-lactide-co-glycolide)). Polyethylene glycol (PEG) and folic acid (FA) via double emulsion solvent evaporation (DESE) method obtained PLGA-EGCG (P-E), PLGA-PEG-EGCG (PP-E), and PLGA-PEG-FA-EGCG (PPF-E). Nanoformulations had been characterized with <sup>1</sup>H NMR and FT-IR techniques, AFM, and DLS. PPF-E NPs showed an average size of 220 nm. Analysis of zeta potential confirmed the stability of NPs. HCT-116, HT-29, HCT-15, and HEK 293 cells were treated with both the prepared NPs and free EGCG (0-140 μM). Result showed PPF-E NPs had improved delivery, uptake and cell cytotoxicity toward human folic acid receptor-positive (FR+) colorectal cancer (CRC) cells as mainly on HCT-116 compared to HT-29, but not on the folic acid-negative cells (FR-) as HCT-15. PPF-E NPs enhanced intracellular reactive oxygen species (ROS) level in absence of N-acetyl-l-cysteine (NAC), elevated DNA fragmentation level, and increased apoptotic cell death at higher doses compared to other two NPs and free EGCG. In conclusion, PPF-E NPs exerted greater efficacy than PP-E, P-E, and free EGCG in HCT-116 cells.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"565-582"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-10-01Epub Date: 2023-11-05DOI: 10.1080/10715762.2023.2277145
J Thomas Brenna, Marina G Sergeeva, Nikolay B Pestov, Tatyana V Korneenko, Mikhail S Shchepinov
{"title":"Arachidonic acid: reconciling the dichotomy of its oxidative cascade through specific deuteration.","authors":"J Thomas Brenna, Marina G Sergeeva, Nikolay B Pestov, Tatyana V Korneenko, Mikhail S Shchepinov","doi":"10.1080/10715762.2023.2277145","DOIUrl":"10.1080/10715762.2023.2277145","url":null,"abstract":"<p><p>A new approach to attenuating pathological inflammatory reactions by buffering the eicosanoid pathways with oxidation-resistant hexadeuterated arachidonic acid (D-ARA) is discussed. Enzymatic processing of ARA, released by phospholipase A2, by lipoxygenases, cyclooxygenases, and cytochromes yields a wide range of bioactive eicosanoids, including pro-inflammation, pro-angiogenesis and pro-thrombosis species that, when produced in excess, are an underlying cause of pathology. Conversely, some products of ARA oxidation possess pro-resolving properties. Non-enzymatic free radical oxidation of ARA generates another large group of products such as isoprostanes and their metabolites, associated with inflammation, ischemia-reperfusion stress, and atherosclerosis. A separate group comprises reactive carbonyl derivatives that irreversibly damage diverse biomolecules. Being resistant to both enzymatic and non-enzymatic oxidation pathways due to large kinetic isotope effects, D-ARA may play a role in mitigating inflammation-related disorders and conditions, including inflammaging.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"583-593"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66783751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-10-01Epub Date: 2023-12-20DOI: 10.1080/10715762.2023.2277142
Karen M Schaich
{"title":"Epoxides: an underestimated lipid oxidation product.","authors":"Karen M Schaich","doi":"10.1080/10715762.2023.2277142","DOIUrl":"10.1080/10715762.2023.2277142","url":null,"abstract":"<p><p>Immense gains in understanding of mechanisms and effects of lipid oxidation have been achieved in the nearly 90 years over which lipid oxidation has been an active research focus. Even so, the substantial questions still being raised about lipid oxidation in this special issue show clearly that missing pieces remain and must be considered for full accounting of this important reaction in any system. In this context, epoxides are spotlighted as a critical overlooked product of lipid autoxidation - underestimated in analysis, underestimated in presence as a functionally active and competitive intermediate and product of lipid oxidation, and underestimated in potential contributions to impact of lipid oxidation on other molecules and cell functions. Logical reasons for ignoring or not finding epoxides are offered in historical development of lipid oxidation knowledge. Reactions generating lipid epoxides in autoxidation are reviewed, limitations in detecting and tracking epoxides are outlined to explain why epoxides may not be detected when they should be present, and justifications for increased research and analysis of epoxides are argued. The main goal is to provide a context for recognizing epoxides as critical products that must be accounted for in determining the state rather than extent of lipid oxidation and in tracking its consequences in oils, foods, personal care products, and tissues. A secondary goal is to stimulate new research using contemporary analyses to fill in the gaps of knowledge about epoxide formation, structure, and reactions in lipid autoxidation.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"517-564"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138829142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-10-01Epub Date: 2024-10-30DOI: 10.1080/10715762.2024.2421173
Ali Sahin, Tugce Demirel-Yalciner, Erdi Sozen, Nesrin Kartal Ozer
{"title":"Protective effect of alpha-tocopherol on lipogenesis and oxysterol production in hypercholesterolemia-induced nonalcoholic steatohepatitis.","authors":"Ali Sahin, Tugce Demirel-Yalciner, Erdi Sozen, Nesrin Kartal Ozer","doi":"10.1080/10715762.2024.2421173","DOIUrl":"10.1080/10715762.2024.2421173","url":null,"abstract":"<p><p>Despite limited number of studies, oxysterols are known to contribute to the progression of nonalcoholic steatohepatitis (NASH) by affecting lipid/cholesterol metabolism and elevating proinflammatory and profibrotic processes. Accordingly, we used a high cholesterol-mediated in vivo NASH model and aimed to determine alterations in fatty acid content and oxysterol levels together with their effects on cholesterol/lipid metabolism during the progression of the disease. We further investigated the beneficial role of α-tocopherol. To this end, in our hypercholesterolemic rabbit model, we determined fatty acid profile by GC-MS while 25-, 27-, 4β-, 7α, and 24(S)-Hydroxycholesterol levels by means of LC-MS/MS. Additionally, lipid (SREBP-1c, PPARα, PPARγ) and cholesterol metabolism-related proteins (LXRα, SREBP2 and ABCA1) were determined by immunoblotting. In conclusion, the present findings provide a complete analysis of the hepatic alterations in lipid and oxysterol profiles mediated by a high-cholesterol diet. In addition, this study explains the protective effect of α-tocopherol on lipogenesis and oxysterol production in hypercholesterolemia-induced NASH. We believe that present study will guide to novel theories in the progression and therapeutic targeting of fatty liver diseases.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"630-640"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Free Radical ResearchPub Date : 2024-10-01Epub Date: 2024-09-24DOI: 10.1080/10715762.2024.2407147
Junichi Fujii
{"title":"Redox remodeling of central metabolism as a driving force for cellular protection, proliferation, differentiation, and dysfunction.","authors":"Junichi Fujii","doi":"10.1080/10715762.2024.2407147","DOIUrl":"10.1080/10715762.2024.2407147","url":null,"abstract":"<p><p>The production of reactive oxygen species (ROS) is elevated <i>via</i> metabolic hyperactivation in response to a variety of stimuli such as growth factors and inflammation. Tolerable amounts of ROS moderately inactivate enzymes <i>via</i> oxidative modification, which can be reversed back to the native form in a redox-dependent manner. The excessive production of ROS, however, causes cell dysfunction and death. Redox-reactive enzymes are present in primary metabolic pathways such as glycolysis and the tricarboxylic acid cycle, and these act as floodgates for carbon flux. Oxidation of a specific form of cysteine inhibits glyceraldehyde-3-phosphate dehydrogenase, which is reversible, and causes an accumulation of upstream intermediary compounds that increases the flux of glucose-6-phosphate to the pentose phosphate pathway. These reactions increase the NADPH and ribose-5-phosphate that are available for reductive reactions and nucleotide synthesis, respectively. On the other hand, oxidative inactivation of mitochondrial aconitase increases citrate, which is then recruited to synthesize fatty acids in the cytoplasm. Decreases in the use of carbohydrate for ATP production can be compensated <i>via</i> amino acid catabolism, and this metabolic change makes nitrogen available for nucleic acid synthesis. Coupling of the urea cycle also converts nitrogen to urea and polyamine, the latter of which supports cell growth. This metabolic remodeling stimulates the proliferation of tumor cells and fibrosis in oxidatively damaged tissues. Oxidative modification of these enzymes is generally reversible in the early stages of oxidizing reactions, which suggests that early treatment with appropriate antioxidants promotes the maintenance of natural metabolism.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"606-629"},"PeriodicalIF":3.6,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}