Schisandrin B Diet Inhibits Oxidative Stress to Reduce Ferroptosis and Lipid Peroxidation to Prevent Pirarubicin‐Induced Hepatotoxicity

Abstract

Objective: Pirarubicin (THP) is one of anthracycline anticancer drugs. It is widely used in the treatment of various cancers, but its hepatotoxicity cannot be ignored. Schisandrin B (SchB) is a traditional liver-protecting drug, which has the ability to promote mitochondrial function and upregulate cellular antioxidant defense mechanism. However, whether it can resist THP-induced hepatotoxicity has not been reported. The purpose of this study was to observe and explore the effect of SchB on THP-induced hepatotoxicity and its potential mechanism by adding SchB to the diet of rats with THP-induced hepatotoxicity. Methods: The rat model of THP-induced hepatotoxicity was established and partly treated with SchB diet. The changes of serum liver function indexes ALT and AST were observed. The histomorphological changes of liver were observed by HE staining. The biomarker levels of oxidative stress in rat serum and liver were measured to observe oxidative stress state. The expressions of ferroptosis-related protein GPX4 and oxidative stress-related protein were detected by Western blot. Primary hepatocytes were prepared and cocultured with THP, SchB, and Fer-1 to detect the production of reactive oxygen species (ROS) and verify the above signal pathways. Results: THP rats showed a series of THP-induced hepatotoxicity changes, such as liver function damage, oxidative stress, and ferroptosis. SchB diet effectively alleviated these adverse reactions. Further studies showed that SchB had strong antioxidant and antiferroptosis abilities in THP-induced hepatotoxicity. Conclusion: SchB has obvious protective effect on THP-induced hepatotoxicity. The mechanism may be closely related to inhibiting oxidative stress and ferroptosis in the liver.