Pub Date : 2025-04-06DOI: 10.1016/j.arres.2025.100130
Wuyan Lu , Jieshen Huang , Zhonglin Zhang , Shuangmeng Jia , Weiqiao Zhao , Linxiao Li , Fengting Niu , Ke Fang , Zixin Cai , Yao Li , Yishu Lu , Lei Cui , Jiefeng Huang , Shuaijun Li
Osteoarthritis (OA) is a prevalent age-related degenerative joint disorder characterized by dysregulation of metabolism. While several studies have examined the metabolic changes in OA, there exists a lack of a comprehensive retrospective analysis of its current development, research hotspots, and future trends. In this study, we employed bibliometric approaches to retrospectively review the development, mechanisms, and future trends of metabolic changes in OA. We utilized VOSviewer software to quantitatively and visually depict: (a) annual temporal trends in literature and citation counts; (b) national/regional publications and collaborations; (c) institutional and author contributions; (d) journal contributions and relevance; (e) analysis of research hotspots and directions through keywords. By analyzing keywords and research hotspots, we systematically illustrated the influential factors of metabolic changes in OA, including inflammation, apoptosis, oxidative stress, and autophagy. Conclusively, the research field of metabolic changes in OA is rapidly expanding, and we aim to provide a more comprehensive and insightful perspective for targeting metabolic disorders in OA.
{"title":"Global hotspots and prospective trends for chondrocyte metabolic changes and oxidative stress in osteoarthritis: A bibliometric analysis","authors":"Wuyan Lu , Jieshen Huang , Zhonglin Zhang , Shuangmeng Jia , Weiqiao Zhao , Linxiao Li , Fengting Niu , Ke Fang , Zixin Cai , Yao Li , Yishu Lu , Lei Cui , Jiefeng Huang , Shuaijun Li","doi":"10.1016/j.arres.2025.100130","DOIUrl":"10.1016/j.arres.2025.100130","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a prevalent age-related degenerative joint disorder characterized by dysregulation of metabolism. While several studies have examined the metabolic changes in OA, there exists a lack of a comprehensive retrospective analysis of its current development, research hotspots, and future trends. In this study, we employed bibliometric approaches to retrospectively review the development, mechanisms, and future trends of metabolic changes in OA. We utilized VOSviewer software to quantitatively and visually depict: (a) annual temporal trends in literature and citation counts; (b) national/regional publications and collaborations; (c) institutional and author contributions; (d) journal contributions and relevance; (e) analysis of research hotspots and directions through keywords. By analyzing keywords and research hotspots, we systematically illustrated the influential factors of metabolic changes in OA, including inflammation, apoptosis, oxidative stress, and autophagy. Conclusively, the research field of metabolic changes in OA is rapidly expanding, and we aim to provide a more comprehensive and insightful perspective for targeting metabolic disorders in OA.</div></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":"15 ","pages":"Article 100130"},"PeriodicalIF":0.0,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799815","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}
Pub Date : 2025-04-02DOI: 10.1016/j.arres.2025.100128
Joseph Mercola
This hypothesis‐driven narrative review delineates the intricate mechanisms by which redox imbalance—encompassing both oxidative and reductive stresses—precipitates mitochondrial dysfunction in metabolic disorders. This review examines how excessive consumption of industrial seed oils rich in linoleic acid (LA) contributes to mitochondrial dysfunction, in part, by promoting peroxidation of lipids, including cardiolipin (CL), and altering mitochondrial bioenergetics. Such modifications destabilize electron transport chain (ETC) supercomplexes and elevate reactive oxygen species (ROS) generation, thereby compromising ATP production and overall mitochondrial efficiency. Additionally, we explore emerging evidence linking LA‐induced mitochondrial perturbations with gut dysbiosis, where impaired colonocyte metabolism disrupts the anaerobic niche critical for microbial balance, further propagating systemic inflammation. An integrative analysis of macronutrient quality and quantity suggests that strategic dietary modulation—particularly a marked reduction in LA intake—may restore mitochondrial redox homeostasis and improve metabolic health. By re-examining historical dietary trends alongside recent biochemical and clinical insights, this work underscores the critical role of mitochondrial membrane dynamics in metabolic pathophysiology and highlights targeted nutritional strategies to preserve mitochondrial integrity.
{"title":"Linoleic acid, mitochondria, gut microbiome, and metabolic health: a mechanistic review","authors":"Joseph Mercola","doi":"10.1016/j.arres.2025.100128","DOIUrl":"10.1016/j.arres.2025.100128","url":null,"abstract":"<div><div>This hypothesis‐driven narrative review delineates the intricate mechanisms by which redox imbalance—encompassing both oxidative and reductive stresses—precipitates mitochondrial dysfunction in metabolic disorders. This review examines how excessive consumption of industrial seed oils rich in linoleic acid (LA) contributes to mitochondrial dysfunction, in part, by promoting peroxidation of lipids, including cardiolipin (CL), and altering mitochondrial bioenergetics. Such modifications destabilize electron transport chain (ETC) supercomplexes and elevate reactive oxygen species (ROS) generation, thereby compromising ATP production and overall mitochondrial efficiency. Additionally, we explore emerging evidence linking LA‐induced mitochondrial perturbations with gut dysbiosis, where impaired colonocyte metabolism disrupts the anaerobic niche critical for microbial balance, further propagating systemic inflammation. An integrative analysis of macronutrient quality and quantity suggests that strategic dietary modulation—particularly a marked reduction in LA intake—may restore mitochondrial redox homeostasis and improve metabolic health. By re-examining historical dietary trends alongside recent biochemical and clinical insights, this work underscores the critical role of mitochondrial membrane dynamics in metabolic pathophysiology and highlights targeted nutritional strategies to preserve mitochondrial integrity.</div></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":"15 ","pages":"Article 100128"},"PeriodicalIF":0.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791261","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}
Pub Date : 2025-03-26DOI: 10.1016/j.arres.2025.100129
Leah N. Falk , William E. Bentley , Deanna L. Kelly , Gregory F. Payne , Eunkyoung Kim
Oxidative stress appears to act globally and span body systems (e.g., nervous, immune, and endocrine). Currently, there is no single, generally-accepted measurement of oxidative stress. Many possible measurement approaches focus on the bottom-up analysis of individual molecules (e.g., reactive species, antioxidants, hormones or signaling molecules) or combinations of molecules (e.g., proteomics or metabolomics). Efforts to develop a global measurement of oxidative stress often detect a sample's ability to reduce a metal-ion (e.g., iron or copper) or quench a free radical. Here, we review results from a recently-developed iridium-reducing capacity assay (Ir-RCA) and suggest that this method offers several key benefits as a potential measurement of oxidative stress. First, the Ir-RCA employs simple optical and/or electrochemical measurements that can be extended to high throughput formats. Second, the Ir-RCA appears to be more sensitive than alternative global antioxidant assays. Third, the Ir-RCA measures stable molecular features of a sample. Fourth, the Ir-RCA has been “validated” by showing statistically significant differences in persons diagnosed with schizophrenia (N = 73) versus healthy controls (N = 45). Fifth, the Ir-RCA measurement of oxidative stress is “movable”: psychosocial stressors can increase this measure of oxidative stress, while beneficial dietary interventions can decrease this measure of oxidative stress. Limitations and future directions for the Ir-RCA are discussed.
{"title":"Measuring oxidative stress by the iridium reducing capacity assay (Ir-RCA)","authors":"Leah N. Falk , William E. Bentley , Deanna L. Kelly , Gregory F. Payne , Eunkyoung Kim","doi":"10.1016/j.arres.2025.100129","DOIUrl":"10.1016/j.arres.2025.100129","url":null,"abstract":"<div><div>Oxidative stress appears to act globally and span body systems (e.g., nervous, immune, and endocrine). Currently, there is no single, generally-accepted measurement of oxidative stress. Many possible measurement approaches focus on the bottom-up analysis of individual molecules (e.g., reactive species, antioxidants, hormones or signaling molecules) or combinations of molecules (e.g., proteomics or metabolomics). Efforts to develop a global measurement of oxidative stress often detect a sample's ability to reduce a metal-ion (e.g., iron or copper) or quench a free radical. Here, we review results from a recently-developed iridium-reducing capacity assay (Ir-RCA) and suggest that this method offers several key benefits as a potential measurement of oxidative stress. First, the Ir-RCA employs simple optical and/or electrochemical measurements that can be extended to high throughput formats. Second, the Ir-RCA appears to be more sensitive than alternative global antioxidant assays. Third, the Ir-RCA measures stable molecular features of a sample. Fourth, the Ir-RCA has been “validated” by showing statistically significant differences in persons diagnosed with schizophrenia (<em>N</em> = 73) versus healthy controls (<em>N</em> = 45). Fifth, the Ir-RCA measurement of oxidative stress is “movable”: psychosocial stressors can increase this measure of oxidative stress, while beneficial dietary interventions can decrease this measure of oxidative stress. Limitations and future directions for the Ir-RCA are discussed.</div></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":"15 ","pages":"Article 100129"},"PeriodicalIF":0.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783060","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}
Pub Date : 2025-03-20DOI: 10.1016/j.arres.2025.100126
Hasnae Boughaleb , Roxane Verdoy , Amandine Pochet , Nathalie Fabian , Ramona Bella , Gopinath Muruganandam , Raphaël Frédérick , Karim Zouaoui Boudjeltia , Axelle Bourez , Cédric Delporte , Pierre Van Antwerpen , Annie Robert , Vincent Haufroid , Joseph P. Dewulf , Jean-Luc Balligand , Virginie Montiel
Objectives
To evaluate the efficacy of Bacopa monnieri (BM) containing Bacopaside II, a specific Aquaporin 1 (AQP1)-blocker, on systemic oxidative stress.
Background
AQP1, is a peroxiporin which facilitates hydrogen peroxide transmembrane passage. It is predominantly expressed in endothelial cells and erythrocytes.
Methods
BM extract was administered orally for 6 weeks to 20 healthy volunteers (Group A/B: 400/800 mg/day). Assessments occurred at baseline (V0), after 6 weeks of treatment (V4), and 4 weeks post-treatment (V6). Primary endpoint: ROS levels in erythrocytes post-H2O2 exposure (DCFDA fluorescence). Secondary endpoints: Oxidative stress and safety biomarkers, blood pressure monitoring. Bacopaside II metabolites in plasma were identified using liquid chromatography-mass spectrometry (LC-MS).
Results
BM intake reduced ROS levels in RBCs in Group B (T40 min: Mean Fluorescence Intensity of DCF V0=381 ± 43 a.u vs V4= 187 ± 69 a.u, p<0.01). Methemoglobin and oxidized Methionine 148 of Apolipoprotein A-1 levels decreased (Methemoglobin group B: V0= 0.900 ± 0.105 a.u vs V4= 0.233 ± 0.047 a.u; p<0.001, M148-ox/M148 ratio group B: V0= 0.06 ± 0.01 a.u. vs V4= 0.02 ± 0.00 a.u.; p<0.05). A reduction in blood pressure was observed in Group B (Systolic Blood Pressure V0=131 ± 15 mmHg vs SBP V4=116 ± 7 mmHg; p < 0.05). Two potential Bacopaside II metabolites with putative binding pockets on AQP1 were identified during the treatment.
Conclusion
A six-week oral intake of BM reduced systemic oxidative stress in healthy volunteers in a dose-dependent manner. Pharmacological blocking of AQP1 may help restore redox balance in the vasculature.
目的观察假马齿苋（Bacopa monnieri， BM）中含有特异性水通道蛋白1 （AQP1）阻断剂bacop皂苷II对全身氧化应激的影响。daqp1是一种促进过氧化氢跨膜通过的过氧化物蛋白。它主要在内皮细胞和红细胞中表达。方法健康志愿者20例（A/B组：400/800 mg/d），口服枸杞提取物6周。评估分别在基线（V0）、治疗6周后（V4）和治疗后4周（V6）进行。主要终点：h2o2暴露后红细胞中的ROS水平（DCFDA荧光）。次要终点：氧化应激和安全生物标志物，血压监测。采用液相色谱-质谱联用技术（LC-MS）对血浆中bacop皂苷II代谢物进行鉴定。结果bm摄入降低B组红细胞ROS水平（T40 min: DCF平均荧光强度V0=381±43 a.u vs V4= 187±69 a.u, p < 0.01）。B组高铁血红蛋白：V0= 0.900±0.105 a.u vs V4= 0.233±0.047 a.u；0.001， M148-ox/M148比值B组：V0= 0.06±0.01 a.u. vs V4= 0.02±0.00 a.u.；术中,0.05)。B组血压降低(收缩压V0=131±15 mmHg vs收缩压V4=116±7 mmHg；p & lt;0.05)。在治疗过程中，发现了两种潜在的Bacopaside II代谢物，这些代谢物可能与AQP1结合。结论连续6周口服BM可降低健康志愿者的全身氧化应激，且呈剂量依赖性。药物阻断AQP1可能有助于恢复血管中的氧化还原平衡。
{"title":"Repurposing Bacopa monnieri extracts containing Aquaporin-1 blockers to improve systemic oxidative stress: The BacOxy_I study","authors":"Hasnae Boughaleb , Roxane Verdoy , Amandine Pochet , Nathalie Fabian , Ramona Bella , Gopinath Muruganandam , Raphaël Frédérick , Karim Zouaoui Boudjeltia , Axelle Bourez , Cédric Delporte , Pierre Van Antwerpen , Annie Robert , Vincent Haufroid , Joseph P. Dewulf , Jean-Luc Balligand , Virginie Montiel","doi":"10.1016/j.arres.2025.100126","DOIUrl":"10.1016/j.arres.2025.100126","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate the efficacy of Bacopa monnieri (BM) containing Bacopaside II, a specific Aquaporin 1 (AQP1)-blocker, on <strong>systemic</strong> oxidative stress.</div></div><div><h3>Background</h3><div>AQP1, is a peroxiporin which facilitates hydrogen peroxide transmembrane passage. It is predominantly expressed in endothelial cells and erythrocytes.</div></div><div><h3>Methods</h3><div>BM extract was administered orally for 6 weeks to 20 healthy volunteers (Group A/B: 400/800 mg/day). Assessments occurred at baseline (V0), after 6 weeks of treatment (V4), and 4 weeks post-treatment (V6). Primary endpoint: ROS levels in erythrocytes post-H<sub>2</sub>O<sub>2</sub> exposure (DCFDA fluorescence). Secondary endpoints: Oxidative stress and safety biomarkers, blood pressure monitoring. Bacopaside II metabolites in plasma were identified using liquid chromatography-mass spectrometry (LC-MS).</div></div><div><h3>Results</h3><div>BM intake reduced ROS levels in RBCs in Group B (T40 min: Mean Fluorescence Intensity of DCF V0=381 ± 43 a.u vs V4= 187 ± 69 a.u, p<0.01). Methemoglobin and oxidized Methionine 148 of Apolipoprotein A-1 levels decreased (Methemoglobin group B: V0= 0.900 ± 0.105 a.u vs V4= 0.233 ± 0.047 a.u; p<0.001, M148-ox/M148 ratio group B: V0= 0.06 ± 0.01 a.u. vs V4= 0.02 ± 0.00 a.u.; p<0.05). A reduction in blood pressure was observed in Group B (Systolic Blood Pressure V0=131 ± 15 mmHg vs SBP V4=116 ± 7 mmHg; p < 0.05). Two potential Bacopaside II metabolites with putative binding pockets on AQP1 were identified during the treatment.</div></div><div><h3>Conclusion</h3><div>A six-week oral intake of BM reduced <strong>systemic</strong> oxidative stress in healthy volunteers in a dose-dependent manner. Pharmacological blocking of AQP1 may help restore redox balance in the vasculature.</div></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":"15 ","pages":"Article 100126"},"PeriodicalIF":0.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799814","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}
Pub Date : 2025-03-19DOI: 10.1016/j.arres.2025.100127
Swaraj Mohanty, Yasmin Ahmad
Chronic and intermittent hypoxia are the two different modalities of developing high-altitude(HA) sickness when an individual is exposed to varying environmental conditions. Exposure to this unusual environment has a great impact on cellular pathophysiology and molecular signaling. The severity of the physiological condition relays on the time and duration of stay at a particular altitude and the workload on an individual. The cellular homeostasis shows a variable trend in different tissues and at the systematic level which needs an in-depth understanding of the possible pharmacological and nonpharmacological management that will be helpful to overcome stressful conditions. In this review article, we have summarized the altered signaling and molecular pathways during chronic and intermittent hypoxia from reported in vitro and in vivo studies on high-altitude exposure and available management strategies.
{"title":"Recent updates on sickness during acute high-altitude hypoxic exposure and its management","authors":"Swaraj Mohanty, Yasmin Ahmad","doi":"10.1016/j.arres.2025.100127","DOIUrl":"10.1016/j.arres.2025.100127","url":null,"abstract":"<div><div>Chronic and intermittent hypoxia are the two different modalities of developing high-altitude(HA) sickness when an individual is exposed to varying environmental conditions. Exposure to this unusual environment has a great impact on cellular pathophysiology and molecular signaling. The severity of the physiological condition relays on the time and duration of stay at a particular altitude and the workload on an individual. The cellular homeostasis shows a variable trend in different tissues and at the systematic level which needs an in-depth understanding of the possible pharmacological and nonpharmacological management that will be helpful to overcome stressful conditions. In this review article, we have summarized the altered signaling and molecular pathways during chronic and intermittent hypoxia from reported in vitro and in vivo studies on high-altitude exposure and available management strategies.</div></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":"15 ","pages":"Article 100127"},"PeriodicalIF":0.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705453","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}
Pub Date : 2025-03-04DOI: 10.1016/j.arres.2025.100124
Krishna Samanta , Ivan Ahel , Pulak Kar
Mitochondrial signalling plays a fundamental role in orchestrating essential intracellular functions, including cellular respiration, proliferation, nucleic acid synthesis, and oxidative stress management. The activation of calpain, a group of Ca2+-dependent cysteine proteases, by ROS-induced oxidative stress is linked to cancer progression. Calpain can be activated by ROS either through intracellular Ca2+ elevation or via oxidative modifications of the protease, altering protein susceptibility to calpain cleavage. In tumour cell biology, ROS-activated calpains influence cell survival, migration, proliferation, apoptosis, and invasiveness. Several studies report unusual calpain expression in cancer cells. Various anticancer drugs induce cytotoxicity by activating calpain, significantly impacting cancer treatment strategies. This unique review explores the perspective of ROS-induced calpain activation and its pivotal role in cancer progression and therapeutics.
{"title":"Deciphering of the reactive oxygen species (ROS) induced calpain activation in cancer progression and its therapeutic potential","authors":"Krishna Samanta , Ivan Ahel , Pulak Kar","doi":"10.1016/j.arres.2025.100124","DOIUrl":"10.1016/j.arres.2025.100124","url":null,"abstract":"<div><div>Mitochondrial signalling plays a fundamental role in orchestrating essential intracellular functions, including cellular respiration, proliferation, nucleic acid synthesis, and oxidative stress management. The activation of calpain, a group of Ca<sup>2+</sup>-dependent cysteine proteases, by ROS-induced oxidative stress is linked to cancer progression. Calpain can be activated by ROS either through intracellular Ca<sup>2+</sup> elevation or via oxidative modifications of the protease, altering protein susceptibility to calpain cleavage. In tumour cell biology, ROS-activated calpains influence cell survival, migration, proliferation, apoptosis, and invasiveness. Several studies report unusual calpain expression in cancer cells. Various anticancer drugs induce cytotoxicity by activating calpain, significantly impacting cancer treatment strategies. This unique review explores the perspective of ROS-induced calpain activation and its pivotal role in cancer progression and therapeutics.</div></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":"15 ","pages":"Article 100124"},"PeriodicalIF":0.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577739","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}
Pub Date : 2025-03-01DOI: 10.1016/j.arres.2025.100123
Hao-Yu Wang , Yu Wang , Shaohua Wu , Jiangong Ma , Xunfeng Zou
Background
Intracellular iron-mediated lipid oxidative damage, referred to as ferroptosis, plays a crucial role in renal ischemia-reperfusion (I/R) injury. This study aims to investigate the effects of a betaine-contained organ preservation solution on renal ferroptosis using the normothermic machine perfusion (NMP) system.
Methods
Healthy adult Bama miniature pigs were utilized in this study. Both kidneys were harvested and stored at 4 °C using three organ preservation solutions: Hypertonic Citrate Adenine (HCA) solution, University of Wisconsin (UW) solution, and modified multiple-saccharide (MS2) solution, for a duration of 24 h. The kidneys were subsequently divided into HCA, UW, and MS groups. The kidneys stored in cold for 2 h were used as a control. All kidneys were reperfused using the NMP system for 2 h. Biochemical indicators and ferroptosis-related markers, including iron levels, oxidative stress, and Acyl-CoA synthetase long-chain family member 4 (ACSL4), were measured.
Results
During the 2-hour NMP, prolonged cold storage and reperfusion significantly induced ferroptosis-mediated renal I/R injury, resulting in severe renal tubular damage. Notably, levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), ACSL4, and iron were significantly elevated in the HCA group compared to the control group (P < 0.05), while these levels were significantly reduced in the UW and MS groups. Additionally, the MS group exhibited results similar to those of the UW group in preventing renal I/R injury.
Conclusion
This study indicates that the betaine-containing MS solution attenuates ferroptosis-mediated renal cold I/R injury by inhibiting oxidative stress.
{"title":"A betaine-contained solution ameliorates cold ischemia reperfusion injury by suppressing ferroptosis in porcine kidney","authors":"Hao-Yu Wang , Yu Wang , Shaohua Wu , Jiangong Ma , Xunfeng Zou","doi":"10.1016/j.arres.2025.100123","DOIUrl":"10.1016/j.arres.2025.100123","url":null,"abstract":"<div><h3>Background</h3><div>Intracellular iron-mediated lipid oxidative damage, referred to as ferroptosis, plays a crucial role in renal ischemia-reperfusion (I/R) injury. This study aims to investigate the effects of a betaine-contained organ preservation solution on renal ferroptosis using the normothermic machine perfusion (NMP) system.</div></div><div><h3>Methods</h3><div>Healthy adult Bama miniature pigs were utilized in this study. Both kidneys were harvested and stored at 4 °C using three organ preservation solutions: Hypertonic Citrate Adenine (HCA) solution, University of Wisconsin (UW) solution, and modified multiple-saccharide (MS2) solution, for a duration of 24 h. The kidneys were subsequently divided into HCA, UW, and MS groups. The kidneys stored in cold for 2 h were used as a control. All kidneys were reperfused using the NMP system for 2 h. Biochemical indicators and ferroptosis-related markers, including iron levels, oxidative stress, and Acyl-CoA synthetase long-chain family member 4 (ACSL4), were measured.</div></div><div><h3>Results</h3><div>During the 2-hour NMP, prolonged cold storage and reperfusion significantly induced ferroptosis-mediated renal I/R injury, resulting in severe renal tubular damage. Notably, levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), ACSL4, and iron were significantly elevated in the HCA group compared to the control group (<em>P</em> < 0.05), while these levels were significantly reduced in the UW and MS groups. Additionally, the MS group exhibited results similar to those of the UW group in preventing renal I/R injury.</div></div><div><h3>Conclusion</h3><div>This study indicates that the betaine-containing MS solution attenuates ferroptosis-mediated renal cold I/R injury by inhibiting oxidative stress.</div></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":"14 ","pages":"Article 100123"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552824","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}
Pub Date : 2025-02-14DOI: 10.1016/j.arres.2025.100121
Robert J. Aitken , Alex Wilkins , Natasha Harrison , Aleona Swegen , Sarah Lambourne
The oxidation of leucomethylene blue (LMB) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) are colorigenic reactions, generating methylene blue (M+) and the ABTS•+ cation radical, respectively. In this study, we have analyzed the conditions under which these probes become oxidized and explored their application in the assessment of antioxidant activity. Using hematin as a catalyst, LMB responded to hydrogen peroxide and cumene hydroperoxide, whereas ABTS could only respond to the latter. However, in the presence of horse radish peroxidase, both probes responded specifically and dose-dependently to hydrogen peroxide. ABTS and LMB could also be oxidized in the anodic chamber of an electrochemical cell, permitting both pre-activation assays of free radical formation and post-activation assessments of free radical scavenging activity. In the pre-activation mode, both ABTS and LMB successfully revealed DMSO's capacity to inhibit free radical formation, in contrast to the ‘green’ solvent Cyrene™, which was virtually devoid of such activity. In the post-activation mode, the LMB oxidation product, methylene blue, was shown to be particularly sensitive to the 2-electron reducing properties of vitamin C. In contrast, ABTS responded more sensitively to compounds, like resveratrol, that used hydrogen atom transfer and one electron reduction to achieve their antioxidant action. Only LMB-based antioxidant assessments correlated with sperm motility (P < 0.001), suggesting this probe's sensitivity to 2-electron reduction may find particular application in diagnostic andrology. Evidently, not all redox sensors are created equal, so in future assessments of antioxidant activity, it will be important to match the chemistry of the probe with its analytical application.
{"title":"Evaluation of leucomethylene blue as a probe for assessing antioxidant activity reveals a potential application in the assessment of male fertility","authors":"Robert J. Aitken , Alex Wilkins , Natasha Harrison , Aleona Swegen , Sarah Lambourne","doi":"10.1016/j.arres.2025.100121","DOIUrl":"10.1016/j.arres.2025.100121","url":null,"abstract":"<div><div>The oxidation of leucomethylene blue (LMB) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) are colorigenic reactions, generating methylene blue (<em>M</em><sup>+</sup>) and the ABTS<sup>•+</sup> cation radical, respectively. In this study, we have analyzed the conditions under which these probes become oxidized and explored their application in the assessment of antioxidant activity. Using hematin as a catalyst, LMB responded to hydrogen peroxide and cumene hydroperoxide, whereas ABTS could only respond to the latter. However, in the presence of horse radish peroxidase, both probes responded specifically and dose-dependently to hydrogen peroxide. ABTS and LMB could also be oxidized in the anodic chamber of an electrochemical cell, permitting both pre-activation assays of free radical formation and post-activation assessments of free radical scavenging activity. In the pre-activation mode, both ABTS and LMB successfully revealed DMSO's capacity to inhibit free radical formation, in contrast to the ‘green’ solvent Cyrene™, which was virtually devoid of such activity. In the post-activation mode, the LMB oxidation product, methylene blue, was shown to be particularly sensitive to the 2-electron reducing properties of vitamin C. In contrast, ABTS responded more sensitively to compounds, like resveratrol, that used hydrogen atom transfer and one electron reduction to achieve their antioxidant action. Only LMB-based antioxidant assessments correlated with sperm motility (<em>P</em> < 0.001), suggesting this probe's sensitivity to 2-electron reduction may find particular application in diagnostic andrology. Evidently, not all redox sensors are created equal, so in future assessments of antioxidant activity, it will be important to match the chemistry of the probe with its analytical application.</div></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":"14 ","pages":"Article 100121"},"PeriodicalIF":0.0,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428163","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}
Pub Date : 2025-02-11DOI: 10.1016/j.arres.2025.100119
Els A. Hartsema , Helen Hemmling , Clare L. Hawkins
Hypohalous acids (HOX) are chemical oxidants that are produced by different mammalian heme peroxidases, which can be released by activated immune cells. These oxidants play an important role in innate immunity, owing to their ability to rapidly kill and detoxify pathogens. However, HOX are also implicated in driving host tissue damage, due to the abundance and over-activation of immune cells in many inflammatory pathologies. Proteins are highly abundant in biological systems and constitute key targets for HOX. These reactions lead to the modification of amino acid side chains, together with protein unfolding, fragmentation and aggregation, which have significant structural and functional effects. This has led to a significant research effort focused on gaining a detailed understanding of the molecular mechanisms involved in HOX-induced protein damage, and how it contributes to the progression of disease and mortality. This review describes the reactivity of HOX with proteins, including the mechanisms involved in the modification of specific amino acid residues, and how this contributes to structural and functional changes. We describe potential pathways by which modification of proteins by HOX contribute to disease and outline some strategies to modulate this type of damage therapeutically.
{"title":"Comparative reactivity of hypohalous acids with proteins: Chemistry, biological effects and consequences","authors":"Els A. Hartsema , Helen Hemmling , Clare L. Hawkins","doi":"10.1016/j.arres.2025.100119","DOIUrl":"10.1016/j.arres.2025.100119","url":null,"abstract":"<div><div>Hypohalous acids (HOX) are chemical oxidants that are produced by different mammalian heme peroxidases, which can be released by activated immune cells. These oxidants play an important role in innate immunity, owing to their ability to rapidly kill and detoxify pathogens. However, HOX are also implicated in driving host tissue damage, due to the abundance and over-activation of immune cells in many inflammatory pathologies. Proteins are highly abundant in biological systems and constitute key targets for HOX. These reactions lead to the modification of amino acid side chains, together with protein unfolding, fragmentation and aggregation, which have significant structural and functional effects. This has led to a significant research effort focused on gaining a detailed understanding of the molecular mechanisms involved in HOX-induced protein damage, and how it contributes to the progression of disease and mortality. This review describes the reactivity of HOX with proteins, including the mechanisms involved in the modification of specific amino acid residues, and how this contributes to structural and functional changes. We describe potential pathways by which modification of proteins by HOX contribute to disease and outline some strategies to modulate this type of damage therapeutically.</div></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":"14 ","pages":"Article 100119"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422629","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}
Pub Date : 2025-02-11DOI: 10.1016/j.arres.2025.100122
Matthew Ryan Smith , Zachery R. Jarrell , Ken H Liu , Choon-Myung Lee , Edward T Morgan , Young-Mi Go , Dean P. Jones
Background
Cigarettes and electronic cigarettes generate many redox-active materials which could impact children's health through second-hand exposures. High-resolution metabolomics methods enable use of non-targeted mass spectrometry of plasma to test for redox consequences of second-hand exposures.
Objectives
Our objectives were to test for oxidative stress metabolites and altered metabolic pathways associated with second-hand exposure to redox-active flavorants and flavorant metabolites in plasma of infants and children.
Methods
Untargeted plasma metabolomics data for infants and children in a population known to include individuals with second-hand exposures to cigarettes and electronic cigarettes were analyzed for cotinine and metabolites of flavorants. A metabolome-wide association study (MWAS) was performed separately for cotinine and menthol glucuronide, derived from the redox-active flavorant, menthol. Pathway enrichment analysis was used to identify metabolic pathways, and xMWAS was used to detect metabolic communities associated with flavorant metabolites.
Results
Menthol glucuronide was one of several flavorant metabolites positively correlated with cotinine. MWAS and pathway enrichment analysis revealed that some pathways associated with both menthol glucuronide and cotinine, while others only associated with menthol glucuronide, including sphingolipid, glycerophospholipid, antioxidant, N-glycan and mitochondrial energy metabolism. 4-hydroxynonenal and other oxidized lipids positively correlated with menthol glucuronide.
Discussion
The results show that flavorants from second-hand electronic cigarette and cigarette exposures in infants and children are associated with changes in redox metabolism which are known to associate with human lung diseases.
{"title":"Redox Metabolomics of Menthol in Children's Plasma with Second-Hand Cigarette and Electronic Cigarette Exposures","authors":"Matthew Ryan Smith , Zachery R. Jarrell , Ken H Liu , Choon-Myung Lee , Edward T Morgan , Young-Mi Go , Dean P. Jones","doi":"10.1016/j.arres.2025.100122","DOIUrl":"10.1016/j.arres.2025.100122","url":null,"abstract":"<div><h3>Background</h3><div>Cigarettes and electronic cigarettes generate many redox-active materials which could impact children's health through second-hand exposures. High-resolution metabolomics methods enable use of non-targeted mass spectrometry of plasma to test for redox consequences of second-hand exposures.</div></div><div><h3>Objectives</h3><div>Our objectives were to test for oxidative stress metabolites and altered metabolic pathways associated with second-hand exposure to redox-active flavorants and flavorant metabolites in plasma of infants and children.</div></div><div><h3>Methods</h3><div>Untargeted plasma metabolomics data for infants and children in a population known to include individuals with second-hand exposures to cigarettes and electronic cigarettes were analyzed for cotinine and metabolites of flavorants. A metabolome-wide association study (MWAS) was performed separately for cotinine and menthol glucuronide, derived from the redox-active flavorant, menthol. Pathway enrichment analysis was used to identify metabolic pathways, and xMWAS was used to detect metabolic communities associated with flavorant metabolites.</div></div><div><h3>Results</h3><div>Menthol glucuronide was one of several flavorant metabolites positively correlated with cotinine. MWAS and pathway enrichment analysis revealed that some pathways associated with both menthol glucuronide and cotinine, while others only associated with menthol glucuronide, including sphingolipid, glycerophospholipid, antioxidant, N-glycan and mitochondrial energy metabolism. 4-hydroxynonenal and other oxidized lipids positively correlated with menthol glucuronide.</div></div><div><h3>Discussion</h3><div>The results show that flavorants from second-hand electronic cigarette and cigarette exposures in infants and children are associated with changes in redox metabolism which are known to associate with human lung diseases.</div></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":"14 ","pages":"Article 100122"},"PeriodicalIF":0.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422630","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}
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