Sesamin protects against Acetaminophen-induced nephrotoxicity by suppressing HMOX1-mediated apoptosis and ferroptosis.

IF 7.4 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Redox Report Pub Date : 2025-12-01 Epub Date: 2025-07-12 DOI:10.1080/13510002.2025.2529695

Siqi Zhu, Jingyi Ren, Yadong Zhang, Xiaoya Sun, Huanting Pei, Bowen Yin, Ziyi Wang, Zhenao Zhang, Shenghe Li, Ruonan Zhang, Ziqian Zeng, Yuxia Ma

{"title":"Sesamin protects against Acetaminophen-induced nephrotoxicity by suppressing HMOX1-mediated apoptosis and ferroptosis.","authors":"Siqi Zhu, Jingyi Ren, Yadong Zhang, Xiaoya Sun, Huanting Pei, Bowen Yin, Ziyi Wang, Zhenao Zhang, Shenghe Li, Ruonan Zhang, Ziqian Zeng, Yuxia Ma","doi":"10.1080/13510002.2025.2529695","DOIUrl":null,"url":null,"abstract":"Background: Acetaminophen (APAP) is a widely used antipyretic and analgesic agent, and acute exposure can lead to renal injury. Sesamin (Ses) is known for its various health benefits. However, it remains unclear whether Ses exerts a protective effect against APAP-induced kidney injury.Methods: In vivo, C57BL/6 mice were pretreated with Ses and injected intraperitoneally with APAP. In vitro, human kidney proximal tubule cells 2 were pretreated with Ses, and then models of kidney injury induced by APAP were established. Kidney damage was evaluated by morphological, inflammation, oxidative stress and protein analyzes.Results: Ses significantly improved APAP-induced nephrotoxicity in vitro and in vivo models. Transcriptomic analysis revealed that the differentially expressed genes were enriched in ferroptosis and apoptosis signaling pathways, identifying heme oxygenase 1 (HMOX1) as a core protein. In the Ses-treated group, ferroptosis and apoptosis were significantly inhibited, while HMOX1 was effectively restored. In cell experiments, both the HMOX1 agonist hemin and Ses attenuated ferroptosis and apoptosis. HMOX1 inhibitor Zinc Protoporphyrin significantly eliminated the protective effect of Ses.Conclusion: Ses alleviates APAP-induced renal injury by mediating the inhibition of ferroptosis and apoptosis via HMOX1. This study provides a new strategy for the prevention and treatment of drug-induced renal injury.","PeriodicalId":21096,"journal":{"name":"Redox Report","volume":"30 1","pages":"2529695"},"PeriodicalIF":7.4000,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258237/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Redox Report","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/13510002.2025.2529695","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/12 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Acetaminophen (APAP) is a widely used antipyretic and analgesic agent, and acute exposure can lead to renal injury. Sesamin (Ses) is known for its various health benefits. However, it remains unclear whether Ses exerts a protective effect against APAP-induced kidney injury.

Methods: In vivo, C57BL/6 mice were pretreated with Ses and injected intraperitoneally with APAP. In vitro, human kidney proximal tubule cells 2 were pretreated with Ses, and then models of kidney injury induced by APAP were established. Kidney damage was evaluated by morphological, inflammation, oxidative stress and protein analyzes.

Results: Ses significantly improved APAP-induced nephrotoxicity in vitro and in vivo models. Transcriptomic analysis revealed that the differentially expressed genes were enriched in ferroptosis and apoptosis signaling pathways, identifying heme oxygenase 1 (HMOX1) as a core protein. In the Ses-treated group, ferroptosis and apoptosis were significantly inhibited, while HMOX1 was effectively restored. In cell experiments, both the HMOX1 agonist hemin and Ses attenuated ferroptosis and apoptosis. HMOX1 inhibitor Zinc Protoporphyrin significantly eliminated the protective effect of Ses.

Conclusion: Ses alleviates APAP-induced renal injury by mediating the inhibition of ferroptosis and apoptosis via HMOX1. This study provides a new strategy for the prevention and treatment of drug-induced renal injury.

查看原文本刊更多论文

芝麻素通过抑制hmox1介导的细胞凋亡和铁凋亡来保护对乙酰氨基酚诱导的肾毒性。

背景：对乙酰氨基酚（APAP）是一种广泛使用的解热镇痛药物，急性暴露可导致肾脏损伤。芝麻素（Ses）以其各种健康益处而闻名。然而，尚不清楚Ses是否对apap诱导的肾损伤具有保护作用。方法：C57BL/6小鼠体内经Ses预处理后，腹腔注射APAP。体外用Ses预处理人肾近端小管细胞2，建立APAP诱导的肾损伤模型。通过形态学、炎症、氧化应激和蛋白分析评估肾脏损伤。结果：在体外和体内模型中，Ses均能显著改善apap引起的肾毒性。转录组学分析显示，差异表达基因在铁凋亡和凋亡信号通路中富集，确定血红素加氧酶1 （HMOX1）为核心蛋白。ses处理组铁下垂和细胞凋亡明显受到抑制，HMOX1得到有效恢复。在细胞实验中，HMOX1激动剂hemin和Ses均能减弱铁下垂和细胞凋亡。HMOX1抑制剂原卟啉锌显著消除了Ses的保护作用。结论：Ses通过HMOX1介导铁下垂和细胞凋亡抑制，减轻apap诱导的肾损伤。本研究为药物性肾损伤的预防和治疗提供了新的策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Redox Report 生物-生化与分子生物学

CiteScore

6.10

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Redox Report is a multidisciplinary peer-reviewed open access journal focusing on the role of free radicals, oxidative stress, activated oxygen, perioxidative and redox processes, primarily in the human environment and human pathology. Relevant papers on the animal and plant environment, biology and pathology will also be included. While emphasis is placed upon methodological and intellectual advances underpinned by new data, the journal offers scope for review, hypotheses, critiques and other forms of discussion.