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

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...

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Main 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
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Redox Report
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Online Access:https://www.tandfonline.com/doi/10.1080/13510002.2025.2529695
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Summary: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.
ISSN:1351-0002
1743-2928