Tetrahydropalmatine significantly attenuated doxorubicin-induced renal injury and improved renal function in mice by activating the SIRT3-mediated Nrf2/HO-1 pathway.
Does Tetrahydropalmatine alleviate doxorubicin-induced renal injury in mouse models?
Tetrahydropalmatine protects against doxorubicin-induced renal injury in preclinical models by activating the SIRT3-mediated Nrf2/HO-1 pathway, reducing oxidative stress, inflammation, and apoptosis.
p-value: p=<0.01
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. 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. THP significantly attenuated DOX-induced renal injury, improved renal function (reduced Scr/BUN), mitigated histopathological/mitochondrial abnormalities, and preserved podocyte integrity. Molecularly, THP upregulates podocyte markers Nephrin/Podocin, enhances antioxidant capacity (increased GSH, SOD, and CAT, decreased MDA), inhibits inflammation (downregulated IL-6, IL-1β, and TNF-α), and suppresses apoptosis (downregulated Bax/caspase-3, upregulated Bcl-2). Notably, both in vivo and in vitro data link THP’s protection to SIRT3-mediated Nrf2/HO-1 pathway activation. THP protects against DOX-induced renal injury in mice. Mechanistically, this may involve activating the SIRT3-mediated Nrf2/HO-1 pathway, improving podocyte function, and inhibiting oxidative stress, inflammation, and apoptosis.
Wang et al. (Thu,) conducted a other in Doxorubicin-induced renal injury (n=40). Tetrahydropalmatine (THP) vs. Doxorubicin (DOX) alone was evaluated on Renal function (UACR, mALB, Scr, and BUN) (p=<0.01). Tetrahydropalmatine significantly attenuated doxorubicin-induced renal injury and improved renal function in mice by activating the SIRT3-mediated Nrf2/HO-1 pathway.