Free Radical Research最新文献

{"title":"Utilization of the nitroxyl radical TEMPOL to assess scavenging activities of lipid-soluble antioxidants against radicals initiated by the thermal decomposition of 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) in ethanol].","authors":"Keizo Takeshita, Ayaka Segawa, Kurumi Tokunaga, Ayaka Inamori, Ayako Matsuo, Yuhei Ohta, Shoko Okazaki","doi":"10.1080/10715762.2025.2531978","DOIUrl":"10.1080/10715762.2025.2531978","url":null,"abstract":"<p><p>To develop a simple and sensitive method for assessing the radical-scavenging activity of lipophilic antioxidants, the decay of the electron spin resonance (ESR) signal of 4-hydroxy-2,2,6,6-tetramethylpiperidine-<i>N</i>-oxyl radical (TEMPOL) was investigated as an indicator of radical reactions. The ESR signal of TEMPOL was decreased in ethanol, but not in acetonitrile, by the pyrolysis of 2,2'-azobis(2,4-dimethylvaleronitrile). Signal decay in ethanol was suppressed by degassing and did not occur in the presence of the spin trapping agent 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-<i>N</i>-oxide (DEPMPO). Spin trapping with DEPMPO showed the formation of peroxyl, alkoxyl, and alkyl radical adducts during the reaction, with peroxyl radical adducts decreasing in the presence of TEMPOL. These results indicate that TEMPOL signal decay occurs by reactions involving ethanol-derived peroxyl radicals. The TEMPOL signal decay was remarkably inhibited by 0.01 mmol/L 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), which is lower than the Trolox concentration used in the ESR-spin trapping method reported previously. Inhibition by methyl gallate was markedly stronger than Trolox, while the effects of 2,6-di-<i>tert</i>-butyl-<i>p</i>-cresol and resveratrol were minor. The order of inhibition of TEMPOL signal decay by antioxidants correlated to some extent with the order of suppression of peroxyl radical adduct formation by DEPMPO spin trapping. Therefore, the peroxyl radical-scavenging activities of lipid-soluble antioxidants may be evaluated with high sensitivity by examining the inhibitory activity of TEMPOL decay caused by radical reactions in ethanol. The measurement time was less than 5 min.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674306","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}

{"title":"Thioredoxin Improves Contact Dermatitis through an Anti-inflammatory Mechanism Different from Glucocorticoids.","authors":"Wang Cuixue, Jinquan Wang, Jiedong Zhou, Zhenbo Gong, Atsushi Fukunaga, Junji Yodoi, Akira Yamauchi, Hai Tian","doi":"10.1080/10715762.2025.2536295","DOIUrl":"https://doi.org/10.1080/10715762.2025.2536295","url":null,"abstract":"<p><p>Thioredoxin (TRX), a redox-regulatory protein of 12 kDa, plays an essential role in modulating oxidative stress and mediating inflammatory processes. In this study, we compared and analyzed the anti-inflammatory effects of topically applied recombinant human TRX (rhTRX), hydrocortisone, and their combination on murine models of contact dermatitis (CD). Topical application of rhTRX, hydrocortisone, and their synergistic combination notably ameliorated ear edema, reduced neutrophilic infiltration within the ear tissues and suppressed the production of cytokines. We explored the distinct anti-inflammatory mechanisms of rhTRX versus hydrocortisone in PMA-induced PAM212 cells. These treatments collectively downregulated the phosphorylation of p-JNK and p-P38 MAPK in the cells. In addition, rhTRX did not impact the proliferation of CD4+ and CD8+ T lymphocytes. Notably, rhTRX directly downregulated macrophage migration inhibitory factor (MIF), whereas it had no effects on the glucocorticoid-induced leucine zipper (GILZ). Collectively, these findings delineated that rhTRX ameliorated contact dermatitis by curtailing MAPK pathway, and enhancing glucocorticoid responsiveness through the targeted downregulation of MIF. Consequently, holds promise as a therapeutic agent for the treatment of contact dermatitis and warrants further investigation in translational research.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-13"},"PeriodicalIF":3.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144663887","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}

{"title":"Redox modulation by a synthetic thiol compound reduces LPS-induced pro-inflammatory cytokine expression in macrophages via AP-1/NLRP3 axis and influences the crosstalk with endothelial cells.","authors":"Sofia Masini, Michela Bruschi, Michele Menotta, Barbara Canonico, Mariele Montanari, Daniela Ligi, Francesca Monittola, Ferdinando Mannello, Giovanni Piersanti, Rita Crinelli, Mauro Magnani, Alessandra Fraternale","doi":"10.1080/10715762.2025.2529914","DOIUrl":"10.1080/10715762.2025.2529914","url":null,"abstract":"<p><p>Perturbation in redox status elicits multiple cellular pathways, including those involved in the inflammatory response. A thiol-based molecule (I-152), releasing N-acetyl-cysteine (NAC) and β-mercaptoethylamine (MEA), was exploited as a redox-modulating agent, and its effects on pro-inflammatory cytokine expression and secretion in lipopolysaccharide (LPS)-stimulated macrophages (MΦ) were investigated. I-152 inhibited cytokine gene expression as well as protein secretion of the most important inflammatory cytokines in three different MΦ models <i>in vitro</i> and <i>ex vivo</i>. It alleviated inflammation <i>via</i> the c-Jun/AP-1 and NF-κB signaling pathways, depending on the dose, and regulated NLRP3 inflammasome expression, leading to decreased IL-1β and IL-18 release and reduced pyroptotic cell death. Consequently, the influence of redox-modulated MΦ secretome on the crosstalk with endothelial cells was evaluated. Co-culture experiments between THP-1 MΦ, that had been pretreated with I-152 before LPS stimulation, and Human Vascular Endothelial Cells (HUVECs) showed reduced VCAM/ICAM expression in these cells in concomitance with a less oxidized and inflamed MΦ proteomic portrait. Overall, our findings suggest that I-152 redox modulation could target the AP-1/NLRP3 axis, affecting LPS-induced inflammation in MΦ and influencing HUVEC responses, revealing a complex and bidirectional interchange.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-19"},"PeriodicalIF":3.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590818","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}

{"title":"Impact of genetic variability on NADPH oxidase activity: An extensive genotype-phenotype assessment.","authors":"Tana Takacova, Markus Anton Schirmer","doi":"10.1080/10715762.2025.2526057","DOIUrl":"https://doi.org/10.1080/10715762.2025.2526057","url":null,"abstract":"<p><strong>Introduction: </strong>Oxidative stress is implicated in various diseases, and the NADPH oxidase enzyme complex (NOX) is a significant source of reactive oxygen species (ROS). Research linking genetic polymorphisms to enzyme activity has produced conflicting results.</p><p><strong>Methods: </strong>We aimed to establish a robust protocol to assess NOX activity in vitro under highly standardized conditions and correlate these measurements with genetic polymorphisms catalogued by the 1000 Human Genome and HapMap projects. Lymphoblastoid cell lines (LCLs) served as a model system with samples from healthy participants from three Caucasian populations. NOX activity stimulated by phorbol 12-myristate 13-acetate was measured using chemiluminescence in 290 LCLs (198 in a training and 92 in a test set) through a series of multiply repeated measurements per LCL comprising in total over 1,500 NOX activity assessments. The association between NOX activity and single nucleotide polymorphisms (SNPs) in the NOX subunit genes <i>CYBA</i>, <i>CYBB</i>, <i>NCF1</i>, <i>NCF2</i>, and <i>NCF4</i> was subsequently examined.</p><p><strong>Results: </strong>Out of 639 valid polymorphic markers, 314 had a minor allele frequency of ≥5%, and 15 SNPs showed a statistically significant correlation with NOX activity in the training set. However, these 15 associations were not confirmed in the test set (all p ≥ 0.1). Additional analyses treating all 290 LCLs as a single cohort yielded three associations at p < 0.01, i.e. CYBA rs1017828, NCF1 rs191081238, and NCF4 rs4821544. However, statistical significance could not be called for any of these genetic markers upon adjustment for multiple testing, regardless whether a co-dominant, dominant or recessive allelic effect was assumed.</p><p><strong>Conclusion: </strong>Our results do not support a reproducible impact of common genetic diversity in NOX subunits on the enzyme activity in subjects of Caucasian origin. This study represents the largest evaluation concerning relationships between NOX genetic variants and enzyme activity to date.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-12"},"PeriodicalIF":3.6,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527088","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}

{"title":"Enhanced cytotoxicity against cancer cells by acetylation of a planar catechin analog.","authors":"Hiromu Ito, Yoshimi Shoji, Yuki Itabashi, Ken-Ichiro Matsumoto, Kei Ohkubo, Kiyoshi Fukuhara, Ikuo Nakanishi","doi":"10.1080/10715762.2025.2525185","DOIUrl":"https://doi.org/10.1080/10715762.2025.2525185","url":null,"abstract":"<p><p>Catechin is a major antioxidant and also shows anti-cancer effect. We have synthesized a catechin analog possessing a planar structure, planar catechin, which has 10-fold larger radical-scavenging activity than the parental (+)-catechin, and demonstrated that the planar catechin showed a significant cytotoxicity in cancer cells. However, the planar catechin has a possibility to lose the innate activity before reaching target cells, because of the higher reactivity with other biological molecules. In this study, we introduced acetyl groups to the phenolic hydroxy groups, which are considered as active sites of the planar catechin, in order to protect from the oxidation of the planar catechin, and examined the effects on cells regarding the toxicity. The acetylated planar catechin showed a remarkable cytotoxicity compared to the original planar catechin, especially in cancer cells, whereas the superoxide scavenging activity of the acetylated planar catechin was weak. On the other hand, after the acetylated planar catechin was treated with esterase, the enhanced superoxide scavenging activity was confirmed by an electron paramagnetic resonance technique. These results indicate that the activity of the planar catechin was maintained by acetylation of the phenolic hydroxy groups and the deprotection by intracellular esterase restored the activity, leading to the induction of the severe cytotoxicity.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-8"},"PeriodicalIF":3.6,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505330","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}

{"title":"Heated tobacco product emissions induce DNA damage in human bronchial epithelial cells via radical formation.","authors":"Michele Davigo, Victoria Claudino Bastos, Kato Mengels, Alex Mommers, Frederik-Jan van Schooten, Jacco J Briedé, Phyllis Jessen, Antoon Opperhuizen, Reinskje Talhout, Sabine A S Langie, Alexander H V Remels","doi":"10.1080/10715762.2025.2521633","DOIUrl":"https://doi.org/10.1080/10715762.2025.2521633","url":null,"abstract":"<p><p>IQOS is a heated tobacco product (HTP) claimed to be less harmful than regular cigarettes. It is unknown whether IQOS emissions contain radicals, cause DNA damage or affect the expression of DNA repair markers in human bronchial epithelial cells. This has important implications as IQOS diffusion is quickly growing, but little toxicological and genotoxic information on its emissions is available. Therefore, we determined the presence of radicals in cigarette smoke extract (CSE) and IQOS extract (IQOSE) by Electron Spin Resonance (ESR) spectroscopy and measured their levels of Tobacco-Specific Nitrosamines (TSNAs) with liquid chromatography-mass spectrometry (LC-MS). Next, DNA damage induced by CSE and IQOSE was determined by means of the Fpg-modified comet assay in human bronchial epithelial cells (BEAS-2B). Finally, the mRNA and protein levels of DNA repair markers in response to both extracts were evaluated. CSE contained significantly more reactive oxygen species (ROS) and TSNAs, whereas more carbon/nitrogen-centered radicals were detected in IQOSE. After 1 h exposure, 3%CSE and 5%IQOSE caused DNA oxidation, while 5%IQOSE also induced DNA strand breaks and alkali-labile sites. Exposure of cells to 1% and 3% IQOSE for 4 h upregulated the expression of DNA repair genes, whereas no significant impact on DNA repair protein levels was observed. This study shows that IQOS extract contains significant amounts of radicals and TSNAs, can induce DNA damage and increase the expression of DNA repair genes in human bronchial epithelial cells. Whether IQOS use is associated with higher risk of developing lung cancer remains to be determined.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-17"},"PeriodicalIF":3.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474464","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}

{"title":"Urinary 8-oxo-7,8-dihydroguanosine as a potential biomarker for the prognosis of acute poisoning patients in the emergency Intensive-care unit: a prospective observational study.","authors":"Ya-Min Dang, Chao-Jie Chen, Ya-Qing Ma, Hong-Lei Liu, Wei Wen, Jin-Hua Quan, Ren-Ai Xu, Jun Dong, Zhong-Qiu Lu, Jian-Ping Cai","doi":"10.1080/10715762.2025.2512463","DOIUrl":"10.1080/10715762.2025.2512463","url":null,"abstract":"<p><p>Acute poisoning remains a significant cause of admission to the emergency intensive-care unit (EICU). Despite a reduced mortality rate, attention is increasingly focusing on the impact of post-intensive-care syndrome (PICS) on readmission. Due to the significant role of oxidative stress (OS) in the pathological mechanisms of poisoning, 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) may hold great potential as biomarkers for OS biomarkers to evaluate the severity and prognosis of poisoning. Therefore, we investigated the longitudinal changes of urinary 8-oxoGuo levels during hospitalization in poisoned patients, their association with organ failure, and their predictive value for 30-day readmission risk. In total, 43 poisoning patients were enrolled from the EICU of the First Affiliated Hospital of Wenzhou Medical University between July 2021 and November 2022. The 30-day readmission rate was 18.6%. Group-based trajectory modeling (GBTM) was used to explore the potential trajectories of urinary OS markers and organ failure scores during hospitalization. Spearman's correlation analysis revealed a significant association between a high trajectory of 8-oxoGuo/creatinine (Cr) and the increased severity of overall organ failure, as well as respiratory and coagulation dysfunctions. Binary logistic regression analysis indicated that a high 8-oxoGuo/Cr trajectory, high respiratory failure score trajectory, and 8-oxoGuo/Cr values at three key points in disease progression (including admission, transfer from EICU, and discharge), along with 8-oxodGuo/Cr levels at admission, were all risk factors for 30-day readmission. The 8-oxoGuo/Cr value at discharge exhibited the best predictive performance. The urinary 8-oxoGuo/Cr ratio may serve as a potential biomarker for prognostic evaluations in patients with poisoning.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"392-408"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144157859","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}

{"title":"Pro-inflammatory properties of M1 phenotypes of human macrophages: prolongation of myeloperoxidase-mediated oxidative stress.","authors":"Maria D Yurkanova, Nastasia V Kosheleva, Arina A Teplova, Peter S Timashev, Irina I Vlasova","doi":"10.1080/10715762.2025.2519528","DOIUrl":"10.1080/10715762.2025.2519528","url":null,"abstract":"<p><p>Macrophages and neutrophils are the main immune cells of the acute stage of inflammation. Upon their activation, membrane-bound NADPH oxidase produces superoxide anion radical, which is converted to H₂O₂ by superoxide dismutase (SOD). In this study, we compared the production of hydrogen peroxide by two phenotypes of pro-inflammatory human M1 macrophages and neutrophils activated with phorbol-12-myristate 13-acetate. Macrophages were obtained from blood monocytes (monocyte-derived macrophages (MDM)) differentiated into MDM using GM- or M-CSF growth factors and polarized into the M1 state, receiving GM_M1, M_M1, respectively. The total level of H₂O₂ production measured in the presence of horseradish peroxidase differed significantly between two types of macrophages. Only GM_M1 macrophages had a level of H₂O₂ production comparable to neutrophils. GM_M1 appear at the site of inflammation after neutrophils, they continue the work of neutrophils in creating a pro-inflammatory environment: they produce several times more H₂O₂ and pro-inflammatory cytokines than M_M1, which arrive at inflammatory site later. Upon activation, MDM_M1 formed big blot-like and smaller dense spheroid-like aggregates. Activated neutrophils secrete the enzyme myeloperoxidase (MPO), which synthesizes the very potent oxidant hypochlorous acid (HOCl) only in the presence of H₂O₂. Neutrophils are short lived cells, MPO can use H₂O₂ produced by activated cultured MDM to synthesize HOCl at physiologically relevant concentrations to prolong oxidative stress.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"452-461"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316308","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}

{"title":"Protective effects of sinensetin against oxidative stress damage induced by AAPH in the brain-gut.","authors":"Tingting Jin, Menghui He, Na Li, Ying He, Feng He","doi":"10.1080/10715762.2025.2514799","DOIUrl":"10.1080/10715762.2025.2514799","url":null,"abstract":"<p><p>Sinensetin (SIN for short) is one of the most common polymethoxyflavonoids found in citrus fruits. Recently, it has been extensively studied due to its ability to prevent or treat a wide range of diseases, including diabetes, obesity, neurological disorders, and cancer. Oxidative stress is closely related to the pathogenesis of many diseases. Based on literature research and the results of our previous experiments, we found that flavonoids have significant antioxidant effects. This study found that sinensetin alleviated AAPH-induced oxidative stress in zebrafish and alleviated intestinal and brain damage (including brain neurons, vascular development, and blood-brain barrier integrity). This study is of great significance for further study of the relationship between gut-brain changes and oxidative stress. This study provides a practical and convenient tool for real-time tracking of the protective effect of natural products on the <i>in vivo</i> oxidative stress model induced by AAPH. In addition, it paves the way for the discovery of more antioxidants in the future.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"409-425"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144208129","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}

{"title":"Dioscin induces ferroptosis to suppress the metastasis of gastric cancer through the SLC7A11/GPX4 axis.","authors":"Doudou Lu, Ling Yuan, Zhaozhao Wang, Duojie Xu, Fandi Meng, Shumin Jia, Yahong Li, Weiqiang Li, Yi Nan","doi":"10.1080/10715762.2025.2515202","DOIUrl":"10.1080/10715762.2025.2515202","url":null,"abstract":"<p><p>The prognosis of gastric cancer (GC) remains poor due to metastases and resistance to chemotherapy. Ferroptosis is a novel cell death regulation mode characterized by iron dependence and lipid peroxidation. Dioscin, a compound extracted from the Paris polyphylla rhizomes roots, has been shown to have an inhibitory effect on cancers. However, whether it induces ferroptosis to participate in anti-cancer metastasis remains unclear. The ability of gastric cancer cells to invade and migrate was evaluated by wound healing and transwell assays. Malondialdehyde (MDA), glutathione (GSH) assay kit, and dichlorofluorescin diacetate (DCFH-DA) fluorescent probes were used to detect ferroptosis in gastric cancer cells. The expression levels of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot methods. The rescue assay was performed by adding Ferrostatin-1 (Fer-1) co-treatment to verify that Dioscin inhibited gastric cancer metastasis by participating in ferroptosis. Dioscin inhibited gastric cancer cells' wound healing, migration, and invasion process. In addition, Dioscin increased the level of reactive oxygen species (ROS) and MDA while decreasing GSH level, and induced ferroptosis of gastric cancer cells. Fer-1, an inhibitor of ferroptosis, could reverse the effect of Dioscin. In terms of mechanism, Dioscin induced ferroptosis through SLC7A11/GPX4 axis and was involved in the regulation of inhibiting metastasis of gastric cancer. These results suggested that Dioscin was involved in anti-cancer metastasis by inducing ferroptosis.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"426-441"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144215327","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}