Tetrahydropalmatine may alleviate doxorubicin-induced renal injury by activating the Sirt3-mediated Nrf2/HO-1 pathway

作者：Wei Wang, Yuanyuan Hu, Yan Xu, Ning Ding, Jiping Wei, Cairong Li, Yong Chen · 发表于：Biology Direct · 年份：2026 · DOI：10.1186/s13062-026-00773-9 · 研究领域：Chemotherapy-induced cardiotoxicity and mitigation、Chemotherapy-induced organ toxicity mitigation、Silymarin and Mushroom Poisoning

Abstract Background Doxorubicin (DOX) is a widely used broad-spectrum chemotherapy drug, but its severe organ toxic and side effects limit its clinical application. Tetrahydropalmatine (THP) protects against DOX-induced renal injury, yet its underlying mechanism remains unclear. This study aimed to verify THP’s protective effect and explore if it acts via the SIRT3-mediated Nrf2/HO-1 signaling pathway. Methods This study adopted an integrated in vivo and in vitro research system to explore the relevant mechanisms. In vivo, a DOX-induced mouse renal injury model was established with THP intervention; renal function was evaluated by detecting serum creatinine (Scr) and blood urea nitrogen (BUN), while renal injury severity was assessed via urine microalbumin (mALB) and urine albumin/creatinine ratio (UACR). Renal histopathological changes including glomerular injury and tubulointerstitial fibrosis were observed, and subcellular structures such as podocyte integrity and mitochondrial morphology were analyzed by transmission electron microscopy (TEM); additionally, the expression of pathway-related proteins was detected. In vitro, a DOX-induced cell injury model was constructed using mouse podocytes (MPC-5), and Western blot and immunofluorescence techniques were employed to determine the expression of key molecules in the Sirt3-Nrf2/HO-1 pathway, combined with in vivo and in vitro experiments to clarify the underlying mechanism. Results THP significantly attenuated DOX-induced r...