Antioxidants & redox signaling最新文献

{"title":"Endothelial Cell-Derived Cholesterol Crystals Promote Endothelial Inflammation in Early Atherogenesis.","authors":"Xia Wang, Wenxia Fu, Guo Zhou, Huanhuan Huo, Xin Shi, Hao Wang, Yinghua Wang, Xiying Huang, Linghong Shen, Long Li, Ben He","doi":"10.1089/ars.2023.0498","DOIUrl":"10.1089/ars.2023.0498","url":null,"abstract":"","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"201-215"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Expression of Lipoic Acid Synthase Aggravates Silica-Induced Pulmonary Fibrosis by Inhibiting the Differentiation of Tregs in Mice.","authors":"Sensen Yan, Yingzheng Zhao, Jingyi Yan, Yabo Guan, Mengdi Lyu, Guangcui Xu, Xuesi Yang, Yichun Bai, Sanqiao Yao","doi":"10.1089/ars.2023.0387","DOIUrl":"10.1089/ars.2023.0387","url":null,"abstract":"<p><p><b><i>Aims:</i></b> In addition to reducing the respiratory function, crystalline silica (SiO₂) disturbs the immune response by affecting immune cells during the progression of silicosis. Regulatory T cell (Treg) differentiation may play a key role in the abnormal polarization of T helper cell (Th)1 and Th2 cells in the development of silicosis-induced fibrosis. Alpha-lipoic acid (ALA) has immunomodulatory effects by promoting Tregs differentiation. Thus, ALA may have a therapeutic potential for treating autoimmune disorders in patients with silicosis. However, little is known regarding whether ALA regulates the immune system during silicosis development. <b><i>Results:</i></b> We found that the expression levels of collagen increased, and the antioxidant capacity was lower in the <i>Lias^-/-</i>+SiO₂ group than in the <i>Lias</i>^+<i>/+</i>+SiO₂ group. The proportion of Tregs decreased in the peripheral blood and spleen tissue in mice exposed to SiO₂. The proportion of Tregs in the <i>Lias^-/-</i>+SiO₂ group was significantly lower than that in the <i>Lias^+/+</i>+SiO₂ group. Supplementary exogenous ALA attenuates the accumulation of inflammatory cells and extracellular matrix in lung tissues. ALA promotes the immunological balance between Th17 and Treg responses during the development of silicosis-induced fibrosis. <b><i>Innovation and Conclusion:</i></b> Our findings confirmed that low expression of lipoic acid synthase aggravates SiO₂-induced silicosis, and that supplementary exogenous ALA has therapeutic potential by improving Tregs in silicosis fibrosis.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"216-232"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Conformational-Dependent Interdomain Redox Relay at the Core of Protein Disulfide Isomerase Activity.","authors":"Eduardo P Melo, Soukaina El-Guendouz, Cátia Correia, Fernando Teodoro, Carlos Lopes, Paulo J Martel","doi":"10.1089/ars.2023.0288","DOIUrl":"10.1089/ars.2023.0288","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Protein disulfide isomerases (PDIs) are a family of chaperones resident in the endoplasmic reticulum (ER). In addition to holdase function, some members catalyze disulfide bond formation and isomerization, a crucial step for native folding and prevention of aggregation of misfolded proteins. PDIs are characterized by an arrangement of thioredoxin-like domains, with the canonical protein disulfide isomerase A1 (PDIA1) organized as four thioredoxin-like domains forming a horseshoe with two active sites, <i>a</i> and <i>a</i>', at the extremities. We aimed to clarify important aspects underlying the catalytic cycle of PDIA1 in the context of the full pathways of oxidative protein folding operating in the ER. <b><i>Results:</i></b> Using two fluorescent redox sensors, redox green fluorescent protein 2 (roGFP2) and HyPer (circularly permutated yellow fluorescent protein containing the regulatory domain of the H₂O₂-sensing protein OxyR), either unfolded or native, as client substrates, we identified the N-terminal <i>a</i> active site of PDIA1 as the main oxidant of thiols. From there, electrons can flow to the C-terminal <i>a</i>' active site, with the redox-dependent conformational flexibility of PDIA1 allowing the formation of an interdomain disulfide bond. The <i>a</i>' active site then acts as a crossing point to redirect electrons to ER downstream oxidases or back to client proteins to reduce scrambled disulfide bonds. <b><i>Innovation and Conclusions:</i></b> The two active sites of PDIA1 work cooperatively as an interdomain redox relay mechanism that explains PDIA1 oxidative activity to form native disulfides and PDIA1 reductase activity to resolve scrambled disulfides. This mechanism suggests a new rationale for shutting down oxidative protein folding under ER redox imbalance. Whether it applies to physiological substrates in cells remains to be shown.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"181-200"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140142676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reactive Oxygen Species Modulation in the Current Landscape of Anticancer Therapies.","authors":"Jiaqi Li, Justin Yi Shen Lim, Jie Qing Eu, Andrew Kieran Ming Hui Chan, Boon Cher Goh, Lingzhi Wang, Andrea Li-Ann Wong","doi":"10.1089/ars.2023.0445","DOIUrl":"10.1089/ars.2023.0445","url":null,"abstract":"<p><p><b><i>Significance:</i></b> Reactive oxygen species (ROS) are generated during mitochondrial oxidative metabolism, and are tightly controlled through homeostatic mechanisms to maintain intracellular redox, regulating growth and proliferation in healthy cells. However, ROS production is perturbed in cancers where abnormal accumulation of ROS leads to oxidative stress and genomic instability, triggering oncogenic signaling pathways on one hand, while increasing oxidative damage and triggering ROS-dependent death signaling on the other. <b><i>Recent Advances:</i></b> Our review illuminates how critical interactions between ROS and oncogenic signaling, the tumor microenvironment, and DNA damage response (DDR) pathways have led to interest in ROS modulation as a means of enhancing existing anticancer strategies and developing new therapeutic opportunities. <b><i>Critical Issues:</i></b> ROS equilibrium exists <i>via</i> a delicate balance of pro-oxidant and antioxidant species within cells. \"Antioxidant\" approaches have been explored mainly in the form of chemoprevention, but there is insufficient evidence to advocate its routine application. More progress has been made <i>via</i> the \"pro-oxidant\" approach of targeting cancer vulnerabilities and inducing oxidative stress. Various therapeutic modalities have employed this approach, including direct ROS-inducing agents, chemotherapy, targeted therapies, DDR therapies, radiotherapy, and immunotherapy. Finally, emerging delivery systems such as \"nanosensitizers\" as radiotherapy enhancers are currently in development. <b><i>Future Directions:</i></b> While approaches designed to induce ROS have shown considerable promise in selectively targeting cancer cells and dealing with resistance to conventional therapies, most are still in early phases of development and challenges remain. Further research should endeavor to refine treatment strategies, optimize drug combinations, and identify predictive biomarkers of ROS-based cancer therapies.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":"322-341"},"PeriodicalIF":5.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Where in the tissues of Danio rerio is more H2O2 produced during acute hypoxia?","authors":"Anastasia D Sergeeva, Anastasiya S Panova, Alexandra D Ivanova, Yulia V Khramova, Ksenia I Morozova, Daria A Kotova, Anastasia V Guryleva, Demid D Khokhlov, Ilya V Kelmanson, Aleksandr V Vasilev, Alexander I Kostyuk, Alexey V Semyanov, Vladimir A Oleinikov, Vsevolod V Belousov, Alexander S Machikhin, Nadezda A Brazhe, Dmitry S Bilan","doi":"10.1089/ars.2024.0563","DOIUrl":"https://doi.org/10.1089/ars.2024.0563","url":null,"abstract":"<p><p>The lack of oxygen (O2) causes changes in the cell functioning. Modeling hypoxic conditions in vitro is challenging given that different cell types exhibit different sensitivities to tissue O2 levels. We present an effective in vivo platform for assessing various tissue and organ parameters in Danio rerio larvae under acute hypoxic conditions. Our system allows simultaneous positioning of multiple individuals within a chamber where O2 level in the water can be precisely and promptly regulated, all while conducting microscopy. We applied this approach in combination with a genetically encoded pH-biosensor SypHer3s and a highly H2O2-sensitive Hyper7 biosensor. Hypoxia causes H2O2 production in areas of brain, heart and skeletal muscles, exclusively in the mitochondrial matrix; it is noteworthy that H2O2 does not penetrate into the cytosol and is neutralized in the matrix upon reoxygenation. Hypoxia causes pronounced tissue acidosis, expressed by a decrease in pH by 0.4-0.6 units everywhere. Using imaging photoplethysmography, we measured in D.rerio fry real-time heart rate decrease under conditions of hypoxia and subsequent reoxygenation. Our observations in this experimental system lead to the hypothesis that mitochondria are the only source of H2O2 in cells of D.rerio under hypoxia.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141858878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peroxiredoxin 3 Deficiency Exacerbates DSS-Induced Acute Colitis via Exosomal miR-1260b-Mediated Barrier Disruption and Proinflammatory Signaling.","authors":"Jing Jin, Moajury Jung, Seong-Keun Sonn, Seungwoon Seo, Joowon Suh, Hyae Yon Kweon, Shin Hye Moon, Huiju Jo, Na Hyeon Yoon, Goo Taeg Oh","doi":"10.1089/ars.2023.0482","DOIUrl":"10.1089/ars.2023.0482","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Peroxiredoxin3 (Prdx3) is an intracellular antioxidant enzyme that is specifically localized in mitochondria and protects against oxidative stress by removing mitochondrial reactive oxygen species (ROS). The intestinal epithelium provides a physical and biochemical barrier that segregates host tissues from commensal bacteria to maintain intestinal homeostasis. An imbalance between the cellular antioxidant defense system and oxidative stress has been implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the role of Prdx3 in the intestinal epithelium under intestinal inflammation has not been elucidated. To investigate the potential role of Prdx3 in intestinal inflammation, we used intestinal epithelial cell (IEC)-specific Prdx3-knockout mice. <b><i>Results:</i></b> IEC-specific Prdx3-deficient mice showed more severe colitis phenotypes with greater degrees of body weight loss, colon shortening, barrier disruption, mitochondrial damage, and ROS generation in IECs. Furthermore, exosomal miR-1260b was dramatically increased in Prdx3-knockdown colonic epithelial cells. Mechanistically, Prdx3 deficiency promoted intestinal barrier disruption and inflammation <i>via</i> P38-mitogen-activated protein kinase/NFκB signaling. <b><i>Innovation:</i></b> This is the first study to report the protective role of Prdx3 in acute colitis using IEC-specific conditional knockout mice. <b><i>Conclusion:</i></b> Our study sheds light on the role of exosome-loaded miRNAs, particularly miR-1260b, in IBD. Targeting miR-1260b or modulating exosome-mediated intercellular communication may hold promise as potential therapeutic strategies for managing IBD and restoring intestinal barrier integrity.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does Deteriorating Antioxidant Defense and Impaired γ-Glutamyl Cycle Induce Oxidative Stress and Hemolysis in Individuals with Sickle Cell Disease?","authors":"Shruti Bhatt, Amit Kumar Mohapatra, Apratim Sai Rajesh, Satyabrata Meher, Alo Nag, Pradip Kumar Panda, Ranjan Kumar Nanda, Suman Kundu","doi":"10.1089/ars.2024.0594","DOIUrl":"10.1089/ars.2024.0594","url":null,"abstract":"<p><p>Sickle cell disease (SCD) affects two-thirds of African and Indian children. Understanding the molecular mechanisms contributing to oxidative stress may be useful for therapeutic development in SCD. We evaluated plasma elemental levels of Indian SCD patients, trait, and healthy controls (<i>n</i> = 10 per group) <i>via</i> inductively coupled plasma mass spectrometry. In addition, erythrocyte metabolomics of Indian SCD and healthy (<i>n</i> = 5 per group) was carried out using liquid chromatography-mass spectrometry. Followed by assessment of antioxidant defense enzymes namely glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT) in erythrocytes and plasma of Indian SCD patients (<i>n</i> = 31) compared with trait (<i>n</i> = 10) and healthy (<i>n</i> = 10). In SCD plasma an elevated plasma ²⁴ Mg, ⁴⁴Ca, ⁶⁶Zn, ²⁰⁸Pb, ³⁹K and reduced ⁵⁷Fe, ⁷⁷Se, and ⁸⁵Rb levels indicated higher hemolysis and anemia. Erythrocyte metabolome of SCD patients clustered separately from healthy revealed 135 significantly deregulated metabolic features, including trimethyllysine, pyroglutamate, glutathione, aminolevulinate, and d-glutamine, indicating oxidative stress and membrane fragility. Repressed GR, SOD, and CAT activities were observed in SCD patients of which GR and CAT activities did not change under hypoxia. These findings lead to the hypothesis that SCD-associated metabolic deregulations and a shift to ATP-consuming aberrant γ-glutamyl cycle leads to anemia, dehydration, oxidative stress, and hemolysis driving the biomechanical pathophysiology of erythrocyte of SCD patients.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disturbance of Fetal Growth by Azithromycin Through Induction of ER Stress in the Placenta.","authors":"Fan Pan, Fan Zhang, Meng-Die Li, YaKun Liang, Wang-Sheng Wang, Kang Sun","doi":"10.1089/ars.2024.0592","DOIUrl":"10.1089/ars.2024.0592","url":null,"abstract":"<p><p><b><i>Aim:</i></b> Azithromycin (AZM) is widely used to treat mycoplasma infection in pregnancy. However, there is no adequate evaluation of its side effect on the placenta. In this study, using human placental syncytiotrophoblasts and a mouse model, we investigated whether AZM use in pregnancy might adversely affect placental function and pregnancy outcome. <b><i>Results:</i></b> Transcriptomic analysis of AZM-treated human placental syncytiotrophoblasts showed increased expression of endoplasmic reticulum (ER) stress-related genes and decreased expression of genes for hormone production and growth factor processing. Verification studies showed that AZM increased the abundance of ER stress mediators (phosphorylated eIF2α, activating transcription factor 4 [ATF4], and C/EBP Homologous Protein [CHOP]) and decreased the abundance of enzymes involved in progesterone and estradiol synthesis (<i>STS</i>, <i>CYP11A1</i>, and <i>CYP19A1</i>) and insulin-like growth factor binding protein (IGFBP) cleavage (<i>PAPPA</i> and <i>ADAM12</i>) in human placental syncytiotrophoblasts. Inhibition of ER stress blocked AZM-induced decreases in the expression of CYP19A1, CYP11A1, PAPPA, and ADAM12, suggesting that the inhibition of AZM on those genes' expression was secondary to AZM-induced ER stress. Further mechanism study showed that increased ATF4 in ER stress might repressively interact with C/EBPα to suppress the expression of those genes, including <i>CEBPA</i> itself. Mouse studies showed that AZM administration decreased fetal weights along with increased ER stress mediators and decreased levels of insulin-like growth factor, estrogen, and progesterone in the maternal blood, which could be alleviated by inhibition of ER stress. <b><i>Innovation and Conclusion:</i></b> These findings first support the fact that AZM, often used during pregnancy, may affect fetal growth by inhibiting crucial enzymes for estrogen and progesterone synthesis and disrupting crucial proteases for IGFBP cleavage <i>via</i> inducing ER stress in placental syncytiotrophoblasts.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superoxide is an Intrinsic Signaling Molecule Triggering Muscle Hypertrophy.","authors":"Siyu Lu, Yiming Zhou, Mincong Liu, Lijun Gong, Li Liu, Zhigui Duan, Keke Chen, Frank J Gonzalez, Fang Wei, Rong Xiang, Guolin Li","doi":"10.1089/ars.2024.0595","DOIUrl":"10.1089/ars.2024.0595","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Redox signaling plays a key role in skeletal muscle remodeling induced by exercise and prolonged inactivity, but it is unclear which oxidant triggers myofiber hypertrophy due to the lack of strategies to precisely regulate individual oxidants <i>in vivo</i>. In this study, we used tetrathiomolybdate (TM) to dissociate the link between superoxide (O₂^•-) and hydrogen peroxide and thereby to specifically explore the role of O₂^•- in muscle hypertrophy in C2C12 cells and mice. <b><i>Results:</i></b> TM can linearly regulate intracellular O₂^•- levels by inhibition of superoxide dismutase 1 (SOD1). A 70% increase in O₂^•- levels in C2C12 myoblast cells and mice is necessary and sufficient for triggering hypertrophy of differentiated myotubes and can enhance exercise performance by more than 50% in mice. SOD1 knockout blocks TM-induced O₂^•- increments and thereby prevents hypertrophy, whereas SOD1 restoration rescues all these effects. Scavenging O₂^•- with antioxidants abolishes TM-induced hypertrophy and the enhancement of exercise performance, whereas the restoration of O₂^•- levels with a O₂^•- generator promotes muscle hypertrophy independent of SOD1 activity. <b><i>Innovation and Conclusion:</i></b> These findings suggest that O₂^•- is an endogenous initiator of myofiber hypertrophy and that TM may be used to treat muscle wasting diseases. Our work not only suggests a novel druggable mechanism to increase muscle mass but also provides a tool for precisely regulating O₂^•- levels <i>in vivo</i>.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141320367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Antioxidant Ergothioneine Alleviates Cisplatin-Induced Hearing Loss through the Nrf2 Pathway.","authors":"Wenji Zhao, Fan Wu, Rui Hu, Jintao Lou, Guisheng Chen, Ziyi Cai, Suijun Chen","doi":"10.1089/ars.2024.0648","DOIUrl":"10.1089/ars.2024.0648","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Cisplatin (CDDP) is a commonly used chemotherapeutic agent for treating head and neck tumors. However, there is high incidence of ototoxicity in patients treated with CDDP, which may be caused by the excessive reactive oxygen species (ROS) generation in the inner ear. Many studies have demonstrated the strong antioxidant effects of ergothioneine (EGT). Therefore, we assumed that EGT could also attenuate cisplatin-induced hearing loss (CIHL) as well. However, the protective effect and mechanism of EGT on CIHL have not been elucidated as so far. In this study, we investigated whether EGT could treat CIHL and the mechanism. <b><i>Results:</i></b> In our study, we confirmed the protective effect of EGT on preventing CDDP-induced toxicity both <i>in vitro</i> and <i>in vivo</i>. The auditory brainstem response threshold shift in the EGT + CDDP treatment mice was 30 dB less than that in the CDDP treatment mice. EGT suppressed production of ROS and proapoptotic proteins both in tissue and cells. By silencing nuclear factor erythroid 2-related factor 2 (Nrf2), we confirmed that EGT protected against CIHL <i>via</i> the Nrf2 pathway. We also found that SLC22A4 (OCTN1), an important molecule involved in transporting EGT, was expressed in the cochlea. <b><i>Innovation:</i></b> Our results revealed the role of EGT in the prevention of CIHL by activating Nrf2/HO-1/NQO-1 pathway, and broadened a new perspective therapeutic target of EGT. <b><i>Conclusion:</i></b> EGT decreased ROS production and promoted the expression of antioxidative enzymes to maintain redox homeostasis in sensory hair cells. Overall, our results indicated that EGT may serve as a novel treatment drug to attenuate CIHL.</p>","PeriodicalId":8011,"journal":{"name":"Antioxidants & redox signaling","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}