Zhu Siqi, Ren Jingyi, Zhang Yadong, Sun Xiaoya, Pei Huanting, Yin Bowen, Wang Ziyi, Zhang Zhenao, Li Shenghe, Zhang Ruonan, Zeng Ziqian, Ma Yuxia
Department of Nutrition and Food Hygiene, School of Public Health, Hebei Medical University, Hebei Key Laboratory of Environment and Human Health, Shijiazhuang, People's Republic of China.
Undergraduate of College of Public Health, Hebei Medical University, Shijiazhuang, People's Republic of China.
Redox Rep. 2025 Dec;30(1):2529695. doi: 10.1080/13510002.2025.2529695. Epub 2025 Jul 12.
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.
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.
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.
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.
对乙酰氨基酚（APAP）是一种广泛使用的解热镇痛药，急性暴露可导致肾损伤。芝麻素（Ses）因其多种健康益处而闻名。然而，Ses是否对APAP诱导的肾损伤具有保护作用仍不清楚。
在体内，C57BL/6小鼠用Ses预处理，然后腹腔注射APAP。在体外，人肾近端小管细胞2用Ses预处理，然后建立APAP诱导的肾损伤模型。通过形态学、炎症、氧化应激和蛋白质分析评估肾损伤。
Ses在体外和体内模型中均显著改善了APAP诱导的肾毒性。转录组分析显示，差异表达基因在铁死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。在Ses治疗组中，铁死亡和凋亡显著受到抑制，而HMOX1得到有效恢复。在细胞实验中，HMOX1激动剂血红素和Ses均减轻了铁死亡和凋亡。HMOX1抑制剂锌原卟啉显著消除了Ses的保护作用。
Ses通过介导HMOX1抑制铁死亡和凋亡来减轻APAP诱导的肾损伤。本研究为药物性肾损伤的防治提供了新策略。
