Redox Biology最新文献

{"title":"Real-time monitoring of ONOO⁻ in cerebral ischemia-reperfusion injury mouse models using a hydrazine-based NIR fluorescent probe","authors":"Jinting Shang ,&nbsp;Yan Yang ,&nbsp;Yaojian Sun ,&nbsp;Wanxia Gao ,&nbsp;Kang Ma ,&nbsp;Chen Wang ,&nbsp;Xin Yu ,&nbsp;Liping Li ,&nbsp;Jiang Zheng ,&nbsp;Na Zhao ,&nbsp;XiJi Shu ,&nbsp;Yibin Zhang","doi":"10.1016/j.redox.2025.103494","DOIUrl":"10.1016/j.redox.2025.103494","url":null,"abstract":"<div><div>Accurate and selective techniques for visualizing endogenous peroxynitrite (ONOO⁻) in cerebral ischemia-reperfusion injury (CIRI) models are essential for understanding its complex pathological processes. Here, we introduced a longwave fluorescent probe <strong>TJO</strong> for detecting ONOO⁻ rapidly and sensitively, with a low detection limit of 91 nM. Furthermore, <strong>TJO</strong> exhibits excellent fluorescence imaging capabilities, enabling detailed visualization of ONOO⁻ in CIRI mice model. This highlights its potential for real-time monitoring of ONOO⁻-related pathological conditions.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103494"},"PeriodicalIF":10.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous hydrogen sulfide persulfidates endothelin type A receptor to inhibit pulmonary arterial smooth muscle cell proliferation","authors":"Yanan Zhang ,&nbsp;Xiaoyu Tian ,&nbsp;Liangyi Chen ,&nbsp;Shiqun Zhao ,&nbsp;Xinjing Tang ,&nbsp;Xin Liu ,&nbsp;Dan Zhou ,&nbsp;Chaoshu Tang ,&nbsp;Bin Geng ,&nbsp;Junbao Du ,&nbsp;Hongfang Jin ,&nbsp;Yaqian Huang","doi":"10.1016/j.redox.2025.103493","DOIUrl":"10.1016/j.redox.2025.103493","url":null,"abstract":"<div><h3>Background</h3><div>The binding of endothelin-1 (ET-1) to endothelin type A receptor (ETAR) performs a critical action in pulmonary arterial smooth muscle cell (PASMC) proliferation leading to pulmonary vascular structural remodeling. More evidence showed that cystathionine γ-lyase (CSE)-catalyzed endogenous hydrogen sulfide (H₂S) was involved in the pathogenesis of cardiovascular diseases. In this study, we aimed to explore the effect of endogenous H₂S/CSE pathway on the ET-1/ETAR binding and its underlying mechanisms in the cellular and animal models of PASMC proliferation.</div></div><div><h3>Methods and results</h3><div>Both live cell imaging and ligand-receptor assays revealed that H₂S donor, NaHS, inhibited the binding of ET-1/ETAR in human PASMCs (HPASMCs) and HEK-293A cells, along with an inhibition of ET-1-activated HPASMC proliferation. While, an upregulated Ki-67 expression by the pulmonary arteries, a marked pulmonary artery structural remodeling, and an increased pulmonary artery pressure were observed in CSE knockout (CSE-KO) mice with a deficient H₂S/CSE pathway compared with those in the wild type (WT) mice. Meanwhile, NaHS rescued the enhanced binding of ET-1 with ETAR and cell proliferation in the CSE-knockdowned HPASMCs. Moreover, the ETAR antagonist BQ123 blocked the enhanced proliferation of CSE-knockdowned HPASMCs. Mechanistically, ETAR persulfidation was reduced in the lung tissues of CSE-KO mice compared to that in WT mice, which could be reversed by NaHS treatment. Similarly, NaHS persulfidated ETAR in HPASMCs and HEK-293A cells. Whereas a thiol reductant dithiothreitol (DTT) reversed the H₂S-induced ETAR persulfidation and further blocked the H₂S-inhibited binding of ET-1/ETAR and HPASMC proliferation. Furthermore, the mutation of ETAR at cysteine (Cys) 69 abolished the persulfidation of ETAR by H₂S, and subsequently blocked the H₂S-suppressed ET-1/ETAR binding and HPASMC proliferation.</div></div><div><h3>Conclusion</h3><div>Endogenous H₂S persulfidated ETAR at Cys69 to inhibit the binding of ET-1 to ETAR, subsequently suppressed PASMC proliferation, and antagonized pulmonary vascular structural remodeling.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103493"},"PeriodicalIF":10.7,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding cataract development in axial myopia: The contribution of oxidative stress and related pathways","authors":"Marta Świerczyńska ,&nbsp;Agnieszka Tronina ,&nbsp;Adrian Smędowski","doi":"10.1016/j.redox.2025.103495","DOIUrl":"10.1016/j.redox.2025.103495","url":null,"abstract":"<div><div>Myopia is an evolving global health challenge, with estimates suggesting that by 2050 it will affect half of the world's population, becoming the leading cause of irreversible vision loss. Moreover, myopia can lead to various complications, including the earlier onset of cataracts. Given the progressive aging of the population and the increase in life expectancy, this will contribute to a rising demand for cataract surgery, posing an additional challenge for healthcare systems. The pathogenesis of nuclear and posterior subcapsular cataract (PSC) development in axial myopia is complex and primarily involves intensified liquefaction of the vitreous body, excessive production of reactive oxygen species, impaired antioxidant defense, and chronic inflammation in the eyeball. These factors contribute to disruptions in mitochondrial homeostasis, abnormal cell signaling, lipid peroxidation, protein and nucleic acid damage, as well as the induction of adverse epigenetic modifications. Age-related and oxidative processes can cause destabilization of crystallins with subsequent protein accumulation, which finally drives to a lens opacification. Moreover, an altered redox status is one of the major contributors to the pathogenesis of PSC. This review aims to summarize the mechanisms known to be responsible for the accelerated development of cataracts in axial myopia and to enhance understanding of these relationships.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103495"},"PeriodicalIF":10.7,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143010689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired lipid homeostasis and elevated lipid oxidation of erythrocyte membrane in adolescent depression","authors":"Jinfeng Wang ,&nbsp;Xiaowen Hu ,&nbsp;Ya Li ,&nbsp;Shuhui Li ,&nbsp;Tianqi Wang ,&nbsp;Dandan Wang ,&nbsp;Yan Gao ,&nbsp;Qian Wang ,&nbsp;Jiansong Zhou ,&nbsp;Chunling Wan","doi":"10.1016/j.redox.2025.103491","DOIUrl":"10.1016/j.redox.2025.103491","url":null,"abstract":"<div><div>Adolescent depression is a globally concerned mental health issue, the pathophysiological mechanisms of which remain elusive. Membrane lipids play a crucial role in brain development and function, potentially serving as a crossroad for the abnormalities in neurotransmitters, neuroendocrine, inflammation, oxidative stress, and energy metabolism observed in depressed adolescents. The primary aim of this study was to investigate the erythrocyte membrane lipid profile in adolescent depression. A total of 2838 erythrocyte membrane lipids were detected and quantified in 81 adolescents with depression and 67 matched healthy adolescents using ultra-high performance liquid chromatography-mass spectrometry. Depressed adolescents exhibited significantly different membrane lipid characteristics compared to healthy controls. Specifically, the levels of cholesterol, sphingomyelins, and ceramides were increased, while ether lipids were decreased in patients. Moreover, the patients showed reduced polyunsaturated fatty acids and elevated lipophilic index in membrane, suggesting diminished membrane fluidity. The higher oxidized membrane lipids and plasma malondialdehyde were observed in adolescent depression, indicating the presence of oxidative stress. Importantly, membrane lipid damage was associated with more severe depressive symptoms and worse cognitive function in patients. In addition, reduced polyunsaturated fatty acids and membrane fluidity may be partly responsible for the blunted niacin skin flushing response found in depressed adolescents. In conclusion, our results reveal impaired erythrocyte membrane lipid homeostasis in adolescents with depression, which may implicate membrane dysfunction in the brain. These findings offer new insights into the underlying molecular mechanisms of adolescent depression, highlighting the potential of counteracting membrane damage as a promising avenue for future therapeutic interventions.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103491"},"PeriodicalIF":10.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11780951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous metabolite N-chlorotaurine attenuates antiviral responses by facilitating IRF3 oxidation","authors":"Yalong Yang,&nbsp;Caiwei Wang,&nbsp;Wenyue Sun,&nbsp;Yue Fu,&nbsp;Xuedong Wu,&nbsp;Chunyuan Zhao,&nbsp;Hui Song,&nbsp;Wei Zhao,&nbsp;Ying Qin","doi":"10.1016/j.redox.2025.103492","DOIUrl":"10.1016/j.redox.2025.103492","url":null,"abstract":"<div><div>Cellular microenvironments critically control the activation of innate immune responses. N-chlorotaurine (Tau-Cl) is an endogenous metabolite that is markedly produced and secreted during pathogenic invasion. However, its effect on the antiviral innate immune responses remains unclear. Here, we demonstrate that viral infection upregulates cellular Tau-Cl level. Tau-Cl attenuates viral infection-induced expression of type I IFNs and facilitates viral replication both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, Tau-Cl facilitates the oxidation of IRF3 at Cys222 and Cys371, a key transcription factor that governs the transcription of type I IFNs. Tau-Cl inhibits phosphorylation and nuclear translocation of IRF3, and blocks IRF3 binding to the IFN-β promoter region. Therefore, we identify Tau-Cl as an endogenous suppressor of IRF3-driven antiviral innate responses and uncover an immune escape mechanism of viruses by affecting host microenvironments.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103492"},"PeriodicalIF":10.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Desflurane attenuates renal ischemia-reperfusion injury by modulating ITGB1/CD9 and reducing oxidative stress in tubular epithelial cells","authors":"Qiaoling Wu,&nbsp;Dongbo Zhang,&nbsp;Siqi Dai,&nbsp;Feifei Liu,&nbsp;Wei Zhang,&nbsp;Tu Shen","doi":"10.1016/j.redox.2025.103490","DOIUrl":"10.1016/j.redox.2025.103490","url":null,"abstract":"<div><h3>Objective</h3><div>Renal ischemia-reperfusion (I/R) injury triggers significant oxidative stress and inflammation, leading to tubular epithelial cell (TEC) damage. This study investigates the protective role of Desflurane (DFE) in renal I/R by modulating the ITGB1/CD9 signaling pathway and mitigating oxidative damage.</div></div><div><h3>Methods</h3><div>Single-cell RNA sequencing (scRNA-seq) and transcriptome analysis identified ITGB1 as a key regulatory gene in TECs during renal I/R. The effects of DFE on ITGB1/CD9 expression were evaluated through <em>in vitro</em> experiments using RT-qPCR, Western blot, and TUNEL assays. A mouse model of renal I/R was employed to assess renal function and oxidative stress markers under DFE treatment.</div></div><div><h3>Results</h3><div>DFE reduced ITGB1 and CD9 expression, resulting in decreased TEC apoptosis and enhanced proliferation. <em>In vivo</em>, DFE-treated mice exhibited improved renal function, with significantly lower serum creatinine and blood urea nitrogen (BUN) levels. Additionally, DFE reduced oxidative stress, as indicated by decreased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, alongside increased superoxide dismutase (SOD) activity.</div></div><div><h3>Conclusion</h3><div>DFE confers renal protection against I/R by modulating the ITGB1/CD9 axis and reducing oxidative stress, offering a promising therapeutic strategy for mitigating kidney damage.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103490"},"PeriodicalIF":10.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosome-equipped TNF antisense oligodeoxynucleotide or 2-deoxy-D-glucose ameliorated nonalcoholic steatohepatitis by modulating superoxide dismutase 1 in mice","authors":"Fei He ,&nbsp;Wei Du ,&nbsp;Yingying Liu ,&nbsp;Yuwei Ling,&nbsp;Ming Xu,&nbsp;Jingjing Liu,&nbsp;Ping Song,&nbsp;Zhiqiang Fang,&nbsp;Zhensheng Yue,&nbsp;Juanli Duan,&nbsp;Lin Wang","doi":"10.1016/j.redox.2025.103488","DOIUrl":"10.1016/j.redox.2025.103488","url":null,"abstract":"<div><div>Inflammatory mediators tumor necrosis factor (TNF) and interleukin 1 beta (IL1β), primarily derived from hepatic macrophages in the liver, play a crucial role in the progression of nonalcoholic steatohepatitis (NASH). Meanwhile, intravenously injected exosomes are mainly distributed in the liver and predominantly taken up by hepatic macrophage. Herein, we aimed to evaluate the feasibility of targeted inhibition of TNF and IL1β expression in hepatic macrophages via exosomes as a potential therapeutic strategy for NASH. In this study, we demonstrated that antisense oligodeoxynucleotide targeting TNF (ASO-TNF) or 2-deoxy-<span>d</span>-glucose (2DG) effectively suppressed the expression of TNF and/or IL1β in macrophages. Exosomes loaded with ASO-TNF or 2DG were able to suppress the expression of TNF and/or IL1β in macrophages <em>in vitro</em> or <em>in vivo</em>. Furthermore, infusion of Exo/ASO-TNF or Exo/2DG significantly attenuated experimental steatohepatitis in choline deficient amino acid-defined (CDAA) or methionine and choline deficient (MCD) diet-fed mice. RNA-seq results showed that treatment with Exo/ASO-TNF or Exo/2DG significantly inhibited pro-inflammatory signaling pathways. Mechanistically, we observed that administration of Exo/ASO-TNF or Exo/2DG could attenuate NASH progression by up-regulating the expression of superoxide dismutase 1 (Sod1). Combined, our findings demonstrated that infusion of exosomes loaded with ASO-TNF or 2DG alleviated experimental steatohepatitis in murine models. Thus, infusion of exosomes loaded with anti-inflammatory agents holds promise as a potential therapeutic strategy for NASH treatment.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103488"},"PeriodicalIF":10.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactive oxygen species: Orchestrating the delicate dance of platelet life and death","authors":"Rui Liao ,&nbsp;Long Wang ,&nbsp;Jing Zeng ,&nbsp;Xiaoqin Tang ,&nbsp;Miao Huang ,&nbsp;Fahsai Kantawong ,&nbsp;Qianqian Huang ,&nbsp;Qibing Mei ,&nbsp;Feihong Huang ,&nbsp;Yan Yang ,&nbsp;Bin Liao ,&nbsp;Anguo Wu ,&nbsp;Jianming Wu","doi":"10.1016/j.redox.2025.103489","DOIUrl":"10.1016/j.redox.2025.103489","url":null,"abstract":"<div><div>Platelets, which are vital for blood clotting and immunity, need to maintain a delicately balanced relationship between generation and destruction. Recent studies have highlighted that reactive oxygen species (ROS), which act as second messengers in crucial signaling pathways, are crucial players in this dance. This review explores the intricate connection between ROS and platelets, highlighting their dual nature. Moderate ROS levels act as potent activators, promoting megakaryocyte (MK) differentiation, platelet production, and function. They enhance platelet binding to collagen, increase coagulation, and directly trigger cascades for thrombus formation. However, this intricate role harbors a double-edged sword. Excessive ROS unleash its destructive potential, triggering apoptosis and reducing the lifespan of platelets. High levels can damage stem cells and disrupt vital redox-dependent signaling, whereas uncontrolled activation promotes inappropriate clotting, leading to thrombosis. Maintaining a precise balance of ROS within the hematopoietic microenvironment is paramount for optimal platelet homeostasis. While significant progress has been made, unanswered questions remain concerning specific ROS signaling pathways and their impact on platelet disorders. Addressing these questions holds the key to unlocking the full potential of ROS-based therapies for treating platelet-related diseases such as thrombocytopenia and thrombosis. This review aims to contribute to this ongoing dialog and inspire further exploration of this exciting field, paving the way for novel therapeutic strategies that harness the benefits of ROS while mitigating their dangers.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103489"},"PeriodicalIF":10.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"De novo lipogenesis protects dormant breast cancer cells from ferroptosis and promotes metastasis","authors":"Beatriz Puente-Cobacho ,&nbsp;Cintia Esteo ,&nbsp;Patricia Altea-Manzano ,&nbsp;Jose Luis Garcia-Perez ,&nbsp;José L. Quiles ,&nbsp;Pedro Sanchez-Rovira ,&nbsp;María D. Martín-Salvago ,&nbsp;Lucía Molina-Jiménez ,&nbsp;Rafael J. Luque ,&nbsp;Sarah-Maria Fendt ,&nbsp;Laura Vera-Ramirez","doi":"10.1016/j.redox.2024.103480","DOIUrl":"10.1016/j.redox.2024.103480","url":null,"abstract":"<div><div>Dormant disseminated tumor cells (DTCs) remain viable for years to decades before establishing a clinically overt metastatic lesion. DTCs are known to be highly resilient and able to overcome the multiple biological hurdles imposed along the metastatic cascade. However, the specific metabolic adaptations of dormant DTCs remain to be elucidated. Here, we reveal that dormant DTCs upregulate <em>de novo</em> lipogenesis and favor the activation and incorporation of monounsaturated fatty acids (MUFAs) to their cellular membranes through the activation of acyl-coenzyme A synthetase long-chain family member 3 (ACSL3). Pharmacologic inhibition of <em>de novo</em> lipogenesis or genetic knockdown of ACSL3 results in lipid peroxidation and non-apoptotic cell death through ferroptosis. Clinically, ACSL3 was found to be overexpressed in quiescent DTCs in the lymph nodes of breast cancer patients and to significantly correlate with shorter disease-free and overall survival. Our work provides new insights into the molecular mechanisms enabling the survival of dormant DTCs and supports the use of <em>de novo</em> lipogenesis inhibitors to prevent breast cancer metastasis.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103480"},"PeriodicalIF":10.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142954090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRIOL attenuates intracerebral hemorrhage injury by bidirectionally modulating microglia- and neuron-mediated hematoma clearance","authors":"CaiLv Wei ,&nbsp;Chen Chen ,&nbsp;ShengLong Li ,&nbsp;YuXuan Ding ,&nbsp;YuWei Zhou ,&nbsp;FangYing Mai ,&nbsp;ShiRan Hong ,&nbsp;JiaXin Wu ,&nbsp;Yang Yang ,&nbsp;Zhu Zhu ,&nbsp;DongDong Xue ,&nbsp;XinPeng Ning ,&nbsp;LongXiang Sheng ,&nbsp;BingZheng Lu ,&nbsp;Wei Cai ,&nbsp;MingJun Yuan ,&nbsp;HuaFeng Liang ,&nbsp;SuiZhen Lin ,&nbsp;GuangMei Yan ,&nbsp;YuPin Chen ,&nbsp;Wei Yin","doi":"10.1016/j.redox.2024.103487","DOIUrl":"10.1016/j.redox.2024.103487","url":null,"abstract":"<div><div>Intracerebral hemorrhage (ICH) represents the most severe subtype of stroke, and the lack of effective clinical pharmacotherapies poses a substantial threat to human health. Hematoma plays a crucial role in determining the prognosis of ICH patients by causing primary mechanical extrusion, followed by secondary brain injuries, such as cerebral edema, iron-mediated oxidative stress, and inflammation resulting from its degradation products. 5α-androst-3β,5α,6β-triol (TRIOL) is a neuroprotective steroid currently undergoing phase II clinical trial for acute ischemic stroke with anti-oxidative and anti-inflammatory properties. However, whether TRIOL can protect brain against ICH injury remains unclear. In this study, we found that TRIOL significantly improved neurological function while reducing hematoma volume, cerebral edema, and tissue damage after ICH. Moreover, TRIOL enhanced microglial hematoma clearance through promoting CD36-mediated erythrophagocytosis and CD163-associated hemoglobin scavenging, while simultaneously reducing the release of microglial inflammatory factors and activating the antioxidative transcription factor Nrf2. Additionally, TRIOL inhibited neuron mediated hematoma absorption by suppressing heme oxygenase 2 (HO-2) and protected neurons against ICH-induced damage in vitro and in vivo. TRIOL also mitigated neuronal iron-dependent oxidative damage by increasing ferritin levels but decreasing divalent metal transporter 1 (DMT1) expression. Overall, these findings highlight the promising potential of TRIOL as a drug candidate for treating ICH.</div></div>","PeriodicalId":20998,"journal":{"name":"Redox Biology","volume":"80 ","pages":"Article 103487"},"PeriodicalIF":10.7,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}