Evaluation of the Hepatoprotective Activity of Silymarin Against Acetaminophen-Induced Oxidative Hepatic Injury in Wistar Rats

Research Article

Abstract

The liver serves as the central hub for the metabolic transformation and detoxification of diverse xenobiotics, rendering it inherently susceptible to chemical-induced pathologies. Acetaminophen (paracetamol) represents a widely utilized analgesic and antipyretic agent that, while safe at therapeutic concentrations, precipitates acute hepatotoxicity when administered at supratherapeutic levels. This injury originates from the metabolic conversion of acetaminophen into N-acetyl-p-benzoquinone imine (NAPQI), a reactive intermediate that depletes hepatic glutathione reservoirs, triggers oxidative stress, and induces hepatocellular necrosis. While N-acetylcysteine remains the primary clinical intervention, its efficacy is often limited by a narrow therapeutic window and potential adverse reactions. Consequently, the search for phytotherapeutic alternatives has identified silymarin, a flavonolignan complex derived from Silybum marianum, as a potent hepatoprotective candidate. Experimental evaluation in male Wistar rats shows that silymarin significantly mitigates hepatic damage induced by acute acetaminophen exposure. Administration of silymarin at doses of 100 mg/kg and 200 mg/kg results in a marked reduction of serum biomarkers, including alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase, while simultaneously restoring endogeneous antioxidant levels. Histopathological analysis corroborates these biochemical findings, revealing a preservation of hepatic architecture and a reduction in centrilobular necrosis. These observations indicate that silymarin exerts its protective effects through robust free-radical scavenging, membrane stabilization, and the stimulation of hepatocyte regeneration. The findings provide substantial evidence for the integration of silymarin as a natural therapeutic strategy for managing drug-induced liver injury