Free Radical Research最新文献

{"title":"4-HNE induces cell death through the VCP-related ubiquitination pathway in diabetic cardiomyopathy and the protective effect of metformin.","authors":"Renshan Liang, Peibin Lin, Dazhong Yin, Ping Wei, Zhanfang Kang","doi":"10.1080/10715762.2026.2665462","DOIUrl":"10.1080/10715762.2026.2665462","url":null,"abstract":"<p><p>Metformin is an approved anti diabetes drug and has potential cardioprotective effects. It is unclear whether the antioxidant effect plays a role in this process. The lipid peroxidation product 4-HNE has been implicated in the pathology of heart diseases, such as diabetic cardiomyopathy, although the exact mechanisms remain unclear. In this study, we identified 4-HNE protein adducts by mass spectrometry in cardiomyocytes, and investigated the mechanism of 4-HNE induced cell death and the protective effect of metformin in cardiomyocytes and diabetic cardiomyopathy models. We found that in the 4-HNE-treated H9C2 cells, 4-HNE covalently binds to the key protein VCP to mediate cardiomyocyte death. 4-HNE also inhibits the ATPase activity of VCP and disrupted its downstream signaling pathway, including increased ubiquitinated protein levels, unfolded protein response, and ultimately leads to cardiomyocyte death. In contrast, overexpression of VCP in H9C2 cardiomyocytes protected 4-HNE induced protein ubiquitination and cell death. Mass spectrometry analysis revealed that 4-HNE binds to VCP at residues K336. In addition, metformin reduced the ubiquitination and death of cardiomyocytes induced by 4-HNE through activation of Nrf2-GSTP1 pathway. In HFD-STZ diabetic cardiomyopathy mice, metformin treatment significantly improved cardiac function, reduced cardiac fibrosis and apoptosis, accompanied by a decrease in the levels of 4-HNE adducts and protein ubiquitination. Overall, our results show that 4-HNE directly binds to VCP and disrupts its signaling pathway, which ultimately leads to cardiomyocyte death. Metformin effectively alleviates the damaging effect of 4-HNE on diabetic cardiomyopathy both in vitro and in vivo, demonstrating potential therapeutic effects.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-19"},"PeriodicalIF":2.9,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766861","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":"Proteomic insights into nepetin-mediated protection against oxidative stress in ARPE-19 cells.","authors":"Xi Chen, Peng Hao, Ping Lu, Ruifang Han, Zhixin Jiang, Li Jiang, Liming Wang, Zunfeng Liu, Xuan Li","doi":"10.1080/10715762.2026.2667438","DOIUrl":"10.1080/10715762.2026.2667438","url":null,"abstract":"<p><p>Oxidative stress is one of the crucial factors associated with the pathogenesis of age-related macular degeneration (AMD), particularly the degeneration of retinal pigment epithelium (RPE) cells. In this study, we identified nepetin, a natural flavonoid compound, as a potential inhibitor of hydrogen peroxide (H₂O₂)-induced ARPE-19 cell death. Pretreatment of nepetin significantly reduced intracellular generation of reactive oxygen species (ROS). Quantitative proteomics was applied to explore the underlying molecular response, revealing that 77 proteins were up-regulated, and 198 proteins were down-regulated significantly after nepetin treatment. Gene ontology (GO) analysis and the protein-protein interaction (PPI) network analysis showed that heme oxygenase 1 (HO-1), Kelch-like ECH-associated protein 1 (KEAP1), Sequestosome 1 (SQSTM1)/p62, and glucose-regulated protein 78 (GRP78) were associated with nepetin-mediated antioxidative responses. Western blotting confirmed the altered expression of these key proteins, with HO-1, p62, and GRP78 being upregulated and KEAP1 being downregulated. Immunofluorescence further showed nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, suggesting the involvement of Nrf2-related antioxidant signaling in nepetin-treated ARPE-19 cells. Although direct causal interactions were not established, the proteomic and bioinformatic analyses provide correlative and suggestive evidence that nepetin modulates key proteins within the oxidative stress response network. Based on our previous research and the current study, nepetin exhibits both anti-inflammatory and antioxidative properties in RPE cells, and may have potential implications for the prophylaxis and treatment of AMD, particularly dry AMD.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-15"},"PeriodicalIF":2.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766871","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":"Fluoxetine alleviates vascular cognitive impairment by activating the Nrf2/ARE pathway via Sp1-mediated OTUD1 transcription.","authors":"Qi Wan, Jingwen Hao, Chanjuan Chen","doi":"10.1080/10715762.2026.2658796","DOIUrl":"10.1080/10715762.2026.2658796","url":null,"abstract":"<p><p>Fluoxetine promotes cerebral angiogenesis and neurogenesis. However, its role in cognitive impairment associated with cerebral small vessel disease (CSVD) remains unclear. The research focused on investigating the influence of fluoxetine on cognitive dysfunction associated with CSVD. An oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 (mouse hippocampal neuronal cell) cell model was created to detect apoptosis, inflammatory factors, and oxidative stress marker levels. A CSVD rat model was established using bilateral common carotid artery occlusion. After being treated with fluoxetine, cognitive impairment, neuronal damage, oxidative stress, and inflammatory factors were assessed in the CSVD rats. The results showed that fluoxetine treatment significantly ameliorated memory, spatial learning, recognition index, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the levels of Nrf2, heme oxygenase-1 (HO-1), and quinone oxidoreductase-1 (NQO-1) in CSVD rats. Fluoxetine reduced hippocampal cell apoptosis rate, pro-apoptotic proteins (Bax and cleaved caspase-3), and proinflammatory factors (TNF-α and IL-1β). Concurrently, it mitigated oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), and reactive oxygen species (ROS). Notably, fluoxetine upregulated the levels of anti-inflammatory cytokine IL-10. Mechanistically, fluoxetine activated the Nrf2/ARE pathway by inhibiting Nrf2 ubiquitination. In addition, fluoxetine promotes OTU domain-containing protein 1 (OTUD1) transcription by activating Sp1, and the OTUD1 knockdown reversed the activation of the Nrf2/ARE pathway by fluoxetine. In conclusion, fluoxetine alleviates CSVD-related cognitive impairment <i>via</i> the Sp1-mediated upregulation of OTUD1 to activate the Nrf2/ARE pathway. This study indicates fluoxetine may have therapeutic potential for CSVD-related cognitive impairment.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-17"},"PeriodicalIF":2.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671868","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":"Oxidation of fluorogenic probes detecting reactive oxygen species in the extracellular medium.","authors":"Małgorzata Rak, Grzegorz Bartosz, Izabela Sadowska-Bartosz","doi":"10.1080/10715762.2026.2665470","DOIUrl":"10.1080/10715762.2026.2665470","url":null,"abstract":"<p><p>Anthocyanins are natural antioxidants that, at low concentrations, are not cytotoxic and do not inhibit cell proliferation <i>in vitro</i> and change color in response to pH changes. An attempt to use anthocyanins as an extracellular indicator instead of Phenol Red showed that changes in the absorption spectrum and an oxidation-sensitive fluorescence band are altered with time in the culture of SKOV-3 cells, but, surprisingly, the changes are more pronounced in the absence than in the presence of cells. To examine the generality of this phenomenon, oxidation of fluorogenic probes used for the detection of reactive oxygen species (ROS), dihydrorhodamine (H₂R 123), dihydroethidium (DHE), and 2',7'-dichlorodihydrofluorescein diacetate (H₂DCF-DA) in cell culture and cell-free media was compared. Comparable or higher oxidation rates in cell-free medium were found for all probes. These results point to autoxidation of redox-active components of the medium as the main cause of changes in the properties of cell culture media and suggest that the intracellular oxidation of the probes may also be partly due to their autoxidation.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-11"},"PeriodicalIF":2.9,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766911","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":"Exogenous 8-hydroxydeoxyguanosine prevents liver fibrosis through the regulation of Rac1-NADPH oxidase signaling in a metabolic dysfunction-associated steatohepatitis model.","authors":"Yoonseok Lee, Ik Soo Kim, Joo Won Kim, Min Kyoung Kim, Yoon Gi Chae, Cheol Soo Choi, Oh Sang Kwon, Yun Soo Kim, Ju Hyun Kim, Dong Hae Chung, Seung Kak Shin","doi":"10.1080/10715762.2026.2668102","DOIUrl":"https://doi.org/10.1080/10715762.2026.2668102","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) progresses to liver fibrosis, cirrhosis, and hepatocellular carcinoma, resulting in increased liver-related mortality. Therefore, developing appropriate drugs for treating MASH and fibrosis using animal models similar to the human phenotype is crucial. The Rac1-NADPH oxidase signaling pathway is a critical mediator of reactive oxygen species (ROS) production in hepatic stellate cells (HSCs), which play a key role in liver fibrosis. Here, we introduce a novel animal model of MASH with liver fibrosis that can be induced similar to humans by short-term fructose-, palmitate-, and cholesterol-rich (FPC) diet and chemicals. We confirmed that exogenous 8-hydroxydeoxyguanosine (8-OHdG) could prevent liver fibrosis by inhibiting Rac1-NADPH oxidase 2 (NOX2) signaling in this MASH model. We found that the new murine MASH model, the FPC diet with 55% glucose/45% fructose solution plus CCl₄ for 12 weeks (FPC + CCl₄ model), could induce proper steatohepatitis and more advanced liver fibrosis than the other established models. Our transcriptomic analysis revealed that the FPC + CCl₄ model displayed metabolic gene signatures similar to those in human MASH. Additionally, exogenous 8-OHdG administration significantly prevented liver fibrosis in the FPC + CCl₄-induced MASH model. 8-OHdG inhibits conditioned medium (CM) from steatotic hepatocyte-induced HSC activation and profibrogenic gene expression by inhibition Rac1 activation, NOX2 expression, and ROS production. In conclusion, our novel FPC + CCl₄ animal model effectively replicated human MASH and fibrosis, offering significant advantages over traditional models. Our findings support the therapeutic potential of 8-OHdG in reducing fibrosis by targeting the Rac1-NOX2 signaling pathway.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-13"},"PeriodicalIF":2.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835740","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":"Physiological and Metabolic Reprogramming of Rice (<i>Oryza sativa</i> L.) under Gamma Irradiation: Insights into Antioxidant Defense and Free Radical Dynamics.","authors":"Chinnasamy Karthiksaran, Prabu Dhinakaran, Arulbalachandran Dhanarajan, Venkatachalam Balamurugan, Kasim Yasmin, Vasudevan Soundarya, S Velu","doi":"10.1080/10715762.2026.2668662","DOIUrl":"https://doi.org/10.1080/10715762.2026.2668662","url":null,"abstract":"<p><p>Rice is a staple food for over 50% of the global population. This study investigated how gamma irradiation affects the metabolic and antioxidant responses in rice. Seeds were exposed to increasing doses of gamma rays (0 to 500 Gy), and their morphological, biochemical, and oxidative responses were evaluated. Germination progressively declined with increasing doses, with maximum inhibition at 500 Gy. The lethal dose (LD₅₀) was determined to be 250 Gy, indicating strong radiosensitivity beyond this level. Growth parameters decreased dose-dependently, implying disrupted cell division and metabolism. Photosynthetic pigments such as chlorophyll a and b decreased at higher doses, while carotenoids peaked at 250 Gy, suggesting a dose-dependent stress response before declining due to ROS-induced damage. Metabolites like carbohydrates, proteins, and amino acids initially increased (peaking at 250 Gy), reflecting stress-adaptive metabolic changes. Proline levels rose consistently with dose, serving as an indicator of stress tolerance. Antioxidant enzymes (CAT, POD, and SOD) showed significant increases, helping mitigate lipid peroxidation (as evidenced by MDA content) and scavenging reactive oxygen species (ROS). Phenolic and flavonoid content also increased, contributing to ROS detoxification. Histochemical staining indicated increased ROS levels, while ESR spectroscopy revealed the formation of irradiation-induced stable radical species, likely representing secondary radicals derived from endogenous biomolecules. FTIR spectroscopy revealed dose-dependent biochemical changes in functional groups of irradiated seeds. Overall, the study highlights that gamma irradiation modulates antioxidant defense and metabolic profiles in rice, enhancing stress adaptation. These findings confirm gamma rays influence ROS management and induce functional and biochemical changes in rice plants.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-25"},"PeriodicalIF":2.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835716","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":"The complementary role of the TRX system in the enzymatic antioxidant defense against iron overload-induced oxidative stress in the mouse kidney.","authors":"Feyza Sönmez Aydın, Berna Hukkamlı, Harun Budak","doi":"10.1080/10715762.2026.2658805","DOIUrl":"10.1080/10715762.2026.2658805","url":null,"abstract":"<p><p>In the present study, we investigated the cooperative role of the TRX/GSH system during the systemic iron accumulation in mouse kidney tissue. Iron accumulation was induced in mice and the total iron content of mouse kidney tissue was determined by spectroscopic method. The expression of <i>Fth1</i>, <i>Fpn1</i>, and <i>Hamp</i> genes were analyzed using qPCR. The results obtained show that the iron overload model is formed. Subsequently, the impact of iron toxicity on Trx system members (Trx1, TrxR1, and Txnip) was examined at the gene and protein expression level, and enzyme activity. Iron toxicity unaffected the Trx system at the gene expression level, but activation of the Trx system was observed at the protein expression level and enzyme activity. Additionally, MDA level, TAS, TOS, and OSI were measured in mouse kidney tissue where oxidative stress was induced by iron toxicity. Finally, the effect of iron supplementation on the activities of GSH system enzymes (GPx, GR, GST) and other enzymatic antioxidants (SOD, CAT) was determined by spectroscopic method. This study demonstrated that SOD and CAT, in particular, protect mouse kidney tissue from iron overload by cooperating with the TRX system against iron toxicity. The effect of iron toxicity on kidney tissue has been shown to differ from that observed in heart and liver tissues in previous studies.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-12"},"PeriodicalIF":2.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728866","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":"Effect of pumpkin polysaccharide-milk combinations on oxidative stress resistance of <i>Caenorhabditis elegans</i> based on Chou-Talalay model.","authors":"Lingli Yang, Yuxuan Tang, Yuxin Kong, Qiqi Yao, Can Xiang, Yuchun Liu, Yuchen Wei, Hongcheng Zhao, Jia Li, Weimin Wang, Yongjun Zhang","doi":"10.1080/10715762.2026.2658787","DOIUrl":"10.1080/10715762.2026.2658787","url":null,"abstract":"<p><p>This study investigated the synergistic antioxidant effects between pumpkin polysaccharide (PPe) and milk to overcome the limitations of single-component efficacy. PPe was prepared <i>via</i> radical-mediated extraction, precipitation, and deproteinization. Combinations of PPe (1.6, 3.2, 4.8 mg·mL^-1) with five commercial milk samples (A-E) were screened using the Chou-Talalay combination index (CI) and DPPH/·OH radical assays. The combination of 1.6 mg mL^-1 PPe with milk A or B exhibited the strongest synergy, with low C_m (median-effect dose) and CI values. In <i>C. elegans</i> under oxidative stress, these optimal combinations significantly extended mean survival time (by 62.85% and 52.34%, respectively) and enhanced endogenous antioxidant defenses (SOD, CAT, GSH). This protective effect was associated with the synergistic upregulation of key antioxidant-related genes, including <i>daf-16</i>, <i>sod-3</i> (insulin/IGF-1 signaling pathway), <i>sir-2.1</i>, and <i>skn-1</i> (Nrf2/KEAP1 pathway). These findings highlight the synergistic antioxidant potential of PPe-milk combinations and provide a theoretical basis for developing functional dairy products.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"1-16"},"PeriodicalIF":2.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671913","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":"Mitochondrial antioxidant enzyme (SOD2) at the crossroads of redox signaling and cancer progression.","authors":"Md Rafikul Islam, Rashedul Alam, Farhadul Islam, Preeti Nagar, Mohammad Alinoor Rahman","doi":"10.1080/10715762.2026.2643692","DOIUrl":"10.1080/10715762.2026.2643692","url":null,"abstract":"<p><p>Normal cells preferably utilize mitochondrial oxidative phosphorylation as the primary source of energy in aerobic conditions. However, superoxide anions (<b>^.</b>O₂<b>^-</b>) are produced as a by-product due to leakage of the electron from the electron transport chain during oxidative phosphorylation, and cells are continuously exposed to elevated levels of superoxide. Superoxide dismutase 2 (SOD2, also called manganese superoxide dismutase or MnSOD) is a mitochondria-matrix-localized antioxidant enzyme that prevents oxidative damage to mitochondria by converting <b>^.</b>O₂<b>^-</b> to hydrogen peroxide (H₂O₂). Previous studies reported the roles of SOD2 in regulating cellular metabolism and the connection of variable SOD2 levels and activity with diverse types and stages of cancer. In this review, we systematically summarize recent findings on the roles of SOD2 in cancer cell proliferation, cell cycle progression, invasion, metastasis, metabolic reprogramming, apoptosis, autophagy, angiogenesis, and immune response. Understanding the regulatory factors and signaling pathways of cancer development and progression mediated by SOD2 could help to target critical cellular vulnerabilities to develop novel therapeutic strategies against cancer.</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"183-200"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermidine improve high copper diet-induced intestinal oxidative stress and microbiota community composition.","authors":"Yuxin Qi, Dongmei Jiang, Shuo Li, Weikang Ling, Xin Wang, Chengweng Ji, Xiaoguang An, Dongmei Li, Xinyi Wang, Bo Kang","doi":"10.1080/10715762.2026.2625094","DOIUrl":"10.1080/10715762.2026.2625094","url":null,"abstract":"<p><p>High copper diet intake detriment animal health and livestock profitability. As a key polyamine, spermidine modulates critical physiological processes, include regulating autophagy and oxidative stress. However, the effect of spermidine in mitigating intestinal oxidative stress triggered by high copper diet has yet to be fully elucidated. In this study, eight-week male C57BL/6J mice were fed either a normal diet or a high-copper diet, supplemented with spermidine through water alone or in combination. The intestinal morphology was analyzed using HE staining, intestinal index, antioxidant capacity, SIgA, the content of copper ion, serum IgA, IgG and D-LA were detection. 16S rRNA was used to assess intestinal microbiota composition. The results showed that high copper diet intake disrupted intestinal morphology, elevated jejunum copper levels by 97% (<i>p</i> < 0.05), increased MDA by 31% and T-AOC by 54% in the duodenum (<i>p</i> < 0.05). Similarly, jejunum MDA increase by 49% and SOD rose by18% (<i>p</i> < 0.05). However, compared to CuSO₄ group, spermidine co-treatment improved duodenum villus-crypt ratio by 37% and enhanced serum IgG and IgA concentrations by 16% and 33% (<i>p</i> < 0.05). Microbial analysis <i>via</i> 16S rRNA sequencing revealed that spermidine reduced <i>Staphylococcus</i> abundance while promoting <i>norank_f_Muribaculaceae</i>. In conclusion, these findings suggest that spermidine supplementation restores intestinal architecture, boosts beneficial microbiota (e.g. <i>Firmicutes, unclassified_f_Lachnospiraceae</i>), and enhances antioxidant markers (SOD, T-AOC) and immune function (IgA).</p>","PeriodicalId":12411,"journal":{"name":"Free Radical Research","volume":" ","pages":"107-116"},"PeriodicalIF":2.9,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146257893","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}