Free Radical Research最新文献

Concurrent erythrocyte glutathione depletion and oxidative shift of the serum thiol-disulfide pool in acute pancreatitis: a case-control study. 急性胰腺炎并发红细胞谷胱甘肽耗竭和血清硫醇-二硫池氧化转移：一项病例对照研究。

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-10-15 DOI: 10.1080/10715762.2026.2750850

Faruk Danış, Murat Alışık

{"title":"Concurrent erythrocyte glutathione depletion and oxidative shift of the serum thiol-disulfide pool in acute pancreatitis: a case-control study.","authors":"Faruk Danış, Murat Alışık","doi":"10.1080/10715762.2026.2750850","DOIUrl":"https://doi.org/10.1080/10715762.2026.2750850","url":null,"abstract":"Oxidative stress is central to acute pancreatitis. Thiol groups drive antioxidant defense in both the extracellular serum thiol-disulfide system and the intracellular glutathione system, yet they have rarely been assessed together in this disease. In a prospective case-control study we enrolled 81 adults with acute pancreatitis and 74 emergency-department controls with non-specific abdominal pain. Serum native and total thiol were measured spectrophotometrically and erythrocyte reduced (GSH) and total glutathione by a colorimetric assay; dynamic disulfide, oxidized glutathione (GSSG), and the ratios were derived. Native thiol was the prespecified primary endpoint. Reduced glutathione (Cohen d = -2.32) and total glutathione (d = -1.83) were lower in patients, and the GSSG/GSH ratio was higher (rank-biserial r = 0.89; all p < 0.001). Native thiol, the primary endpoint, was also lower (d = -1.14; p < 0.001), as was total thiol (d = -0.78), whereas dynamic disulfide (d = 1.24) and the disulfide/total thiol ratio (d = 2.04) were higher. The differences persisted in patients without any comorbidity and within each sex. Severe disease showed moderately lower native and total thiol than mild disease (d = -0.78 and -0.69), but no severity comparison survived correction for multiple testing. Both thiol-based antioxidant compartments were therefore disturbed in acute pancreatitis: the erythrocyte glutathione pool was depleted and oxidized, and the serum thiol pool, most of which resides on albumin, was lower and shifted toward disulfide. The largest change was in the glutathione compartment, and only the serum markers showed a preliminary association with severity.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-14"},"PeriodicalIF":3.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192606","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}

引用次数: 0

TRIM25 promotes neuronal ferroptosis in ischemic stroke by suppressing YBX1/H3K4me1/FTH1 axis. TRIM25通过抑制YBX1/H3K4me1/FTH1轴促进缺血性卒中神经元铁凋亡。

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-10-13 DOI: 10.1080/10715762.2026.2748965

Kaimin Zeng, Jing-Jing Peng, Ziwei Lan, Da Gao, Pei Zhu, Zihao Zhu, Yan Li

{"title":"TRIM25 promotes neuronal ferroptosis in ischemic stroke by suppressing YBX1/H3K4me1/FTH1 axis.","authors":"Kaimin Zeng, Jing-Jing Peng, Ziwei Lan, Da Gao, Pei Zhu, Zihao Zhu, Yan Li","doi":"10.1080/10715762.2026.2748965","DOIUrl":"https://doi.org/10.1080/10715762.2026.2748965","url":null,"abstract":"Background: Ferroptosis impairs neurological function in ischemic stroke (IS). This study elucidated the mechanism by which Tripartite motif 25 (TRIM25) promotes neuronal ferroptosis during IS.Methods: CCK-8 detected cell viability. Flow cytometry and corresponding kits quantified ferroptosis-related parameters. TTC staining determined cerebral infarct volume. Neurological impairment was assessed using neurological deficit scoring and Nissl staining. RT-qPCR, Western blot, and immunohistochemistry assessed the mRNA and protein expression. Co-IP analyzed the ubiquitinated level of Y-box binding protein 1 (YBX1) and the interaction between TRIM25 and YBX1. ChIP assessed the binding of YBX1 and H3K4me1 at the Ferritin heavy chain 1 (FTH1) promoter. Peptide pull-down assessed the interaction between YBX1 and H3K4me1.Results: TRIM25 promoted neuronal ferroptosis in IS. TRIM25 promoted YBX1 ubiquitination and degradation. YBX1 knockdown counteracted the suppressive outcome of TRIM25 depletion on OGD/R-induced ferroptosis. YBX1 upregulated FTH1 by recognizing H3K4me1 enrichment at the FTH1 promoter, thus inhibiting OGD/R-induced neuronal ferroptosis. In vivo, TRIM25 knockdown attenuated MCAO/R-induced brain injury via YBX1 upregulation.Conclusion: TRIM25 induces YBX1 ubiquitination and degradation, impairing YBX1-dependent H3K4me1 enrichment at the FTH1 promoter to downregulate FTH1, thereby promoting neuronal ferroptosis in IS.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-46"},"PeriodicalIF":3.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180434","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}

引用次数: 0

Longitudinal urinary 8-oxoGuo as a potential biomarker of persistent risk during ICU and post-ICU hospitalization. 纵向尿8-氧过作为ICU和ICU后住院期间持续风险的潜在生物标志物

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-09-28 DOI: 10.1080/10715762.2026.2736770

Chao-Jie Chen, Ren-Ai Xu, Guang-Liang Hong, Hong-Lei Liu, Jin-Hua Quan, Xi Chen, Ya-Min Dang, Ya-Qing Ma, Ran Huan, Wei Wen, Zhong-Qiu Lu, Jian-Ping Cai

{"title":"Longitudinal urinary 8-oxoGuo as a potential biomarker of persistent risk during ICU and post-ICU hospitalization.","authors":"Chao-Jie Chen, Ren-Ai Xu, Guang-Liang Hong, Hong-Lei Liu, Jin-Hua Quan, Xi Chen, Ya-Min Dang, Ya-Qing Ma, Ran Huan, Wei Wen, Zhong-Qiu Lu, Jian-Ping Cai","doi":"10.1080/10715762.2026.2736770","DOIUrl":"10.1080/10715762.2026.2736770","url":null,"abstract":"Persistent biological injury may remain undetected despite apparent clinical stabilization during critical illness. We evaluated whether serial urinary markers of RNA and DNA oxidation were associated with 90-day mortality, transition from ICU to post-ICU phase, and mortality after ICU discharge, and whether they provided prognostic information beyond baseline illness severity. This single-center longitudinal cohort included 438 critically ill adults who provided 2,516 urine samples during ICU and post-ICU hospitalization. Urinary 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) were quantified by isotope-dilution ultra-performance liquid chromatography-tandem mass spectrometry and normalized to creatinine. Bayesian joint models were adjusted for age, sex, Charlson Comorbidity Index, and baseline Sequential Organ Failure Assessment (SOFA) score. Each doubling of longitudinal urinary 8-oxoGuo was associated with higher 90-day mortality (hazard ratio [HR], 1.47; 95% credible interval [CrI], 1.17-1.85), higher mortality after ICU discharge (HR, 1.52; 95% CrI, 1.18-1.97), and a lower transition rate to post-ICU care (HR, 0.89; 95% CrI, 0.79-0.99). Associations were similar when APACHE II replaced SOFA, whereas longitudinal 8-oxodGuo showed no consistent associations. Adding baseline 8-oxoGuo to SOFA increased the area under the curve for 90-day mortality from 0.669 to 0.719 (p = 0.046), while incorporating longitudinal trajectory information increased the area under the curve for mortality after ICU discharge from 0.682 to 0.741 (p = 0.029). Overall, these findings indicate that higher longitudinal urinary 8-oxoGuo is associated with adverse outcomes across ICU and post-ICU hospitalization and provides incremental prognostic discrimination beyond baseline SOFA.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-10"},"PeriodicalIF":3.1,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149059732","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}

引用次数: 0

Piperine prevents N-nitrosodiethylamine-induced hepatocarcinogenesis via modulating oxidative stress and gap junction. 胡椒碱通过调节氧化应激和间隙连接阻止n -亚硝基二乙胺诱导的肝癌发生。

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-09-23 DOI: 10.1080/10715762.2026.2735947

Sachin Shetty, Anushree U, Rajesh Kumar, Sanjay Bharati

{"title":"Piperine prevents N-nitrosodiethylamine-induced hepatocarcinogenesis via modulating oxidative stress and gap junction.","authors":"Sachin Shetty, Anushree U, Rajesh Kumar, Sanjay Bharati","doi":"10.1080/10715762.2026.2735947","DOIUrl":"10.1080/10715762.2026.2735947","url":null,"abstract":"Phytochemicals are shown to exhibit strong chemopreventive potential which is mediated by simultaneously targeting oxidative stress and different cellular pathways. In this study, we investigated modulatory effect of piperine in N-Nitrosodiethylamine (NDEA)-induced hepatocarcinogenesis. Study was conducted at 2 stages of hepatocarcinogenesis: initiation stage (after 24 h of NDEA administration) and progression stage (after 20 weeks of NDEA administration). Hepatocarcinogenesis mouse model was developed by administration of NDEA intraperitoneally (200 mg/kg bw, cumulative dose) at weekly intervals to male BALB/c mice. Piperine was administered orally (50 mg/kg bw, dissolved in corn oil) weekly twice, till completion of the study. The protective effect on piperine in NDEA-induced liver damage was evident during initiation phase of the study as piperine treatment normalized liver injury markers, ROS levels and modulated carcinogen biotransformation enzymes. During progression stage of carcinogenesis, piperine treatment showed decreased tumor incidence and multiplicity. The dielectric parameters of the tumors also indicated impeded tumor progression. Gap junction expressions deteriorated and modulated during carcinogenesis was normalized by piperine treatment. In conclusion, piperine showed significant protection against hepatocarcinogenesis both at initiation and progression stage.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-13"},"PeriodicalIF":3.1,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148988597","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}

引用次数: 0

ABTS^•+ radical cation-based new potentiometric approach for the studying of antioxidant capacity. ABTS•+自由基阳离子电位法研究抗氧化能力的新方法。

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-09-21 DOI: 10.1080/10715762.2026.2733534

Elena Gerasimova, Elena Salimgareeva, Elizaveta Rybina, Alla Ivanova

{"title":"ABTS•+ radical cation-based new potentiometric approach for the studying of antioxidant capacity.","authors":"Elena Gerasimova, Elena Salimgareeva, Elizaveta Rybina, Alla Ivanova","doi":"10.1080/10715762.2026.2733534","DOIUrl":"10.1080/10715762.2026.2733534","url":null,"abstract":"The potentiometric approach for the studying of total antioxidant capacity, based on the use of the cation radical of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), is proposed. Conditions for non-enzymatic generation that enable the formation of a cation radical/reduced form system, subsequently employed as a potential-determining system, have been established. The ratio of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) to ammonium persulfate was 1:0.5; the solvent was 0.1 M KCl and ethanol (1:1); generation (25 ± 2 °C) was carried out for 24 h. It was shown that the system remains stable in the solid state for at least one month after drying at 70 °C. Individual antioxidants, plant extracts, and model biological fluids were investigated using the developed potentiometric approach. No statistically significant differences were observed between the results obtained by the classical spectrophotometric method and the proposed potentiometric method; the F- and t-tests did not exceed their critical values. Plant extracts with initial coloration and a model whole blood sample were investigated in the absorption range of the ABTS cation radical, which had previously been problematic using spectrophotometry.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-10"},"PeriodicalIF":3.1,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963259","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}

引用次数: 0

The role of overdose folic acid in promoting neuroinflammation, oxidative stress, and apoptosis in SOD1-G93A mice. 过量叶酸对SOD1-G93A小鼠神经炎症、氧化应激和细胞凋亡的促进作用

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-09-10 DOI: 10.1080/10715762.2026.2729677

Yanbo Zhu, Yalun Zhang, Taotao Yan, Yongbo Li, Haikuan Du, Shuang Zhang, Tonghe Zhang, Wei Zhou

{"title":"The role of overdose folic acid in promoting neuroinflammation, oxidative stress, and apoptosis in SOD1-G93A mice.","authors":"Yanbo Zhu, Yalun Zhang, Taotao Yan, Yongbo Li, Haikuan Du, Shuang Zhang, Tonghe Zhang, Wei Zhou","doi":"10.1080/10715762.2026.2729677","DOIUrl":"10.1080/10715762.2026.2729677","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a neurodegenerative condition that involves the targeted degeneration of motor neurons. The precise pathogenetic mechanisms are still largely unclear. In this study, we utilized the SOD1-G93A mouse model of ALS to investigate the effects of folic acid (FA), an important factor involved in homocysteine metabolism. Our results indicated that a little FA prolonged the lifespan of the SOD1-G93A mice and medium and high-dose FA significantly shortened the lifespan of the SOD1-G93A mice. Furthermore, we observed that an overdose of FA significantly elevated inflammation levels in the cerebellum, as evidenced by increased concentrations of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), cluster of differentiation 68 (CD68), cluster of differentiation 86 (CD86), and monocyte chemoattractant protein-1 (MCP-1), facilitating microglial activation. The low-dose FA effects were the opposite of the overdose FA. Additionally, high-dose FA increased the levels of phosphorylated p65 (p-p65)/p65, thereby promoting the NF-κB signaling pathway. Conversely, high-dose FA inhibited the expression of total superoxide dismutase (T-SOD) while increasing the level of malondialdehyde (MDA) in the cerebellum; these effects were not observed in muscle tissue. Moreover, high-dose FA elevated the levels of Bax2/Bcl-2. Concurrently, high-dose FA induced increased apoptosis in SOD1-G93A mice, as demonstrated by TUNEL staining. Notably, the brain iron content of SOD1-G93A mice remained unchanged following FA treatment. These findings provide evidence that an overdose of FA supplementation may exert pro-inflammatory effects by promoting the NF-κB pathway, oxidative stress, and apoptosis in the context of ALS.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.1,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896671","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}

引用次数: 0

Heat shock protein 70 protects against peroxynitrite-induced inactivation of the cardiac sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA2a). 热休克蛋白70对过氧亚硝酸盐诱导的心脏sarco（endo）质网Ca2+- atp酶（SERCA2a）失活具有保护作用。

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-09-04 DOI: 10.1080/10715762.2026.2727872

Chris Vigna, Minghua Fu, Aeron Humaid, A Russell Tupling

{"title":"Heat shock protein 70 protects against peroxynitrite-induced inactivation of the cardiac sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a).","authors":"Chris Vigna, Minghua Fu, Aeron Humaid, A Russell Tupling","doi":"10.1080/10715762.2026.2727872","DOIUrl":"10.1080/10715762.2026.2727872","url":null,"abstract":"Peroxynitrite (ONOO-) is a reactive nitrogen species implicated in oxidative injury and impaired calcium handling. We examined whether ONOO- inactivates the cardiac sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a) and whether heat shock protein 70 (Hsp70) preserves SERCA2a function during ONOO- exposure. Human embryonic kidney (HEK-293) cells were co-transfected with SERCA2a and either empty pMT2 vector (S2a-pMT2) or Hsp70 (S2a-Hsp70). Cells were untreated or exposed to ten nominal 250 μM additions of ONOO-, delivered once per minute for 10 min. Hsp70 abundance was greater in S2a-Hsp70 cells, although the magnitude of this difference varied by treatment (interaction, p = 0.0015). SERCA2a abundance was unaffected by transfection condition or ONOO- exposure. Co-immunoprecipitation showed that Hsp70 and SERCA2a were present in the same protein complex under the conditions examined. ONOO- reduced maximal SERCA2a activity by approximately 20% in S2a-pMT2 cells (p = 0.03), whereas activity was preserved in S2a-Hsp70 cells. ONOO- also increased SERCA2a-associated reactive carbonyl content by approximately 80% in S2a-pMT2 cells (p = 0.01), with no increase in S2a-Hsp70 cells. SERCA2a 3-nitrotyrosine content and FITC-binding capacity did not differ among groups. These findings show that Hsp70 overexpression preserves SERCA2a activity during acute ONOO- exposure and that this protection is associated with reduced SERCA2a carbonyl accumulation.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.1,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873542","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}

引用次数: 0

Sensitive electrochemical and hepatoprotective assessment of polyphenols in Echinacea purpurea-based pharmaceutical products. 紫锥菊类药物中多酚的电化学敏感性及肝保护评价。

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-08-24 DOI: 10.1080/10715762.2026.2719745

Aboelhasan G Shehata, Asmaa S Abbas, Nagwa Mohammed El-Sawi, Emad F Newair

{"title":"Sensitive electrochemical and hepatoprotective assessment of polyphenols in Echinacea purpurea-based pharmaceutical products.","authors":"Aboelhasan G Shehata, Asmaa S Abbas, Nagwa Mohammed El-Sawi, Emad F Newair","doi":"10.1080/10715762.2026.2719745","DOIUrl":"10.1080/10715762.2026.2719745","url":null,"abstract":"This study utilizes a sensitive electrochemical method to investigate the polyphenolic content and antioxidant properties of three pharmaceutical products derived from Echinacea purpurea-Immunvita, Immulone, and C-Mune. An analytical evaluation was conducted with a glassy carbon electrode serving as the working electrode, a silver/silver chloride electrode as the reference, and a platinum wire as the counter electrode. Voltammetric analysis was employed to examine the characteristics of standard caffeic acid and the pharmaceutical samples within a citrate-phosphate electrolyte buffer. Results indicated a high antioxidant capacity and polyphenolic content within the products. Voltammetry proved to be an effective and sensitive approach for quantifying the total polyphenolic content and assessing the antioxidant activity of E. purpurea extracts. Furthermore, the hepatoprotective effects of these pharmaceuticals against lead acetate-induced liver injury were evaluated in Wistar rats. Fifty adult male rats were divided into five groups. Group I, the control; Group II was subjected to oral administration of 60 mg/kg body weight (B.W) of lead acetate for one week; Groups III, IV, and V received the same initial treatment as Group II, followed by a 10-day administration of 105 mg/kg BW Immunvita, 75 mg/kg BW Immulone, or 50 mg/kg BW C-Mune, respectively. Lead acetate ingestion elevated serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT). Co-administration of the examined pharmaceuticals significantly mitigated the elevation of liver enzymes, demonstrating their potential for hepatoprotective effects. Serum ALT levels remained above control values after treatment, likely due to persistent hepatocyte injury or the limited duration of supplementation.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-16"},"PeriodicalIF":3.1,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790396","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}

引用次数: 0

Melatonin alleviates ferroptosis and rescues osteogenic function in iron-overloaded BMSCs via suppressing NOX4 transcription. 褪黑素通过抑制NOX4转录减轻铁超载骨髓间充质干细胞的铁下垂和恢复成骨功能。

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-08-14 DOI: 10.1080/10715762.2026.2718328

Cen Luo, Na Sun, Fei Xiong, Jingjing Sun, Jing Jin, Xin Shao, Lei Xi

{"title":"Melatonin alleviates ferroptosis and rescues osteogenic function in iron-overloaded BMSCs via suppressing NOX4 transcription.","authors":"Cen Luo, Na Sun, Fei Xiong, Jingjing Sun, Jing Jin, Xin Shao, Lei Xi","doi":"10.1080/10715762.2026.2718328","DOIUrl":"10.1080/10715762.2026.2718328","url":null,"abstract":"Iron overload‑induced osteoporosis (IOO) is a growing concern, yet the underlying mechanisms remain obscure. Ferroptosis, an iron‑dependent lipid peroxidation‑driven cell death, and NADPH oxidase 4 (NOX4), a major source of reactive oxygen species (ROS), have been implicated separately, but their interplay in bone marrow stromal cells (BMSCs) under iron overload is unknown. Here we investigated whether melatonin, an endogenous indole with antioxidant properties, protects BMSCs from iron overload‑induced ferroptosis and osteogenic dysfunction by regulating NOX4 transcription. BMSCs were exposed to ferric ammonium citrate (FAC, 200 µM) with or without melatonin (100 µM) or the ferroptosis inhibitor ferrostatin‑1 (Fer‑1). FAC suppressed cell viability, elevated Fe2+ and ROS, triggered classical ferroptotic mitochondrial damage (shrinkage, cristae loss), and impaired osteogenic differentiation (ALP activity, mineralization, Alp, Runx2, Col1a1, Osterix). Fer‑1 attenuated ROS and mitochondrial injury but did not reduce Fe2+ accumulation, confirming ferroptosis downstream of iron loading. Melatonin did not lower Fe2+ levels either; however, it effectively quenched ROS, restored mitochondrial ultrastructure, and rescued osteogenic function. Mechanistically, melatonin transcriptionally suppressed NOX4, as evidenced by reduced NOX4 mRNA and diminished NOX4 promoter activity in dual‑luciferase reporter assays, without affecting Fe2+ levels. Collectively, melatonin alleviates ferroptosis and restores osteogenesis in iron‑overloaded BMSCs, an effect that is strongly associated with the transcriptional suppression of NOX4, independent of iron chelation. Our findings extend the established NOX4-ferroptosis mechanism to BMSCs and identify, for the first time, transcriptional suppression of NOX4 as a novel mechanism that is strongly indicated to contribute to melatonin's protective effects against iron overload-induced osteogenic dysfunction.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-14"},"PeriodicalIF":3.1,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720111","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}

引用次数: 0

Chemical repair, regeneration, and the role of superoxide in antioxidant activity. 化学修复、再生和超氧化物在抗氧化活性中的作用。

IF 3.1 3区生物学

Free Radical Research Pub Date : 2026-08-07 DOI: 10.1080/10715762.2026.2712426

Juan Raúl Alvarez-Idaboy

{"title":"Chemical repair, regeneration, and the role of superoxide in antioxidant activity.","authors":"Juan Raúl Alvarez-Idaboy","doi":"10.1080/10715762.2026.2712426","DOIUrl":"10.1080/10715762.2026.2712426","url":null,"abstract":"Antioxidant activity is commonly discussed in fields like chemistry, biology, nutrition, and medicine, but it is often viewed in functional terms rather than as a process controlled by basic radical kinetics. In many cases, antioxidant efficiency is described within a simple scavenging model, where antioxidants mainly intercept reactive radicals stoichiometrically and are then irreversibly consumed. While this model highlights an important aspect of antioxidant behavior, it does not fully capture the complexity of oxidative processes. In this review, antioxidant chemistry is examined as a competitive reaction network where chemical repair and regeneration pathways play a key mechanistic role. These pathways allow for the restoration of radical intermediates before damage terminates and enable the recycling of oxidized antioxidant species, thus extending antioxidant activity beyond just radical trapping. In this context, the identity of radicals, branching ratios, oxygen-dependent competition, and radical lifetimes are crucial factors that determine whether oxidative processes lead to propagation, termination, or repair. Special focus is given to phenolic antioxidants and to reaction networks involving the hydroperoxyl/superoxide couple (HO2•/O2•-). Although superoxide is often described as a weak oxidant or a precursor to more reactive species, its reactivity depends heavily on conditions. Under the right kinetic conditions, superoxide can participate in reductive pathways that contribute to antioxidant regeneration and radical repair. By combining insights from radiation chemistry, electrochemistry, and computational kinetics, this review highlights chemical repair as an important mechanistic component of antioxidant activity and offers a unified framework for understanding antioxidant function in various chemical and biological settings.","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-24"},"PeriodicalIF":3.1,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630012","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}

引用次数: 0