Co-Therapy of Silymarin and Vitamin E Attenuates Doxorubicin-Induced Hepatotoxicity in Rats by Mitigating Oxidative Damage and Preserving Hepatic Architecture

Abstract

Background: Doxorubicin (DOX) is one of the most potent anthracycline antibiotics that is widely used in oncology. Its clinical use is greatly limited by dose-dependent toxicities, including hepatotoxicity which is caused by oxidative stress and inflammation.

Objective: This study investigated whether the combining of silymarin (a polyphenolic flavonolignan) and vitamin E (a lipophilic membrane antioxidant) had exerted hepatoprotective effects against DOX-induced liver injury in rats.

Methods: 48 male Wistar rats were assigned into six groups, including a negative control, a DOX control (15 mg/kg cumulative intraperitoneal dose), and treatment groups receiving silymarin 200 mg/kg, vitamin E 200 mg/kg, or their combination, and recovery group. Liver injury was assessed by measuring tissue biomarkers for oxidative stress (MDA, SOD), inflammation (IL-6), and apoptosis (Caspase-3, Bax, Bcl-2) and serum biomarkers (AST, ALT, ALP, TSB), while histological analysis was used to assess necrosis, fatty degeneration, fibrosis, and inflammatory cell infiltration.

Results: In this study DOX administration caused severe liver injury, evidenced by significant increase in hepatic MDA, IL-6, and Caspase-3, alongside depleted SOD and Bcl-2 levels. The combination therapy restored oxidative, inflammatory, and apoptotic markers close to the normal levels more effectively than monotherapy.

Conclusion: The administration of silymarin and vitamin E  concurrently offers greater protection against DOX-induced hepatotoxicity through a synergistic mechanism involving antioxidant regeneration and membrane stabilization.