Comparison of the Protective Effects of N-Acetylcysteine and Silymarin in an Acetaminophen-Induced Hepatotoxicity Model

Acetaminophen (APAP) is a widely used analgesic and antipyretic agent; however, high-dose exposure may result in severe hepatotoxicity. The toxic effects of acetaminophen are mediated by the formation of the reactive metabolite N-acetyl-p-benzoquinone imine, leading to depletion of hepatic glutathione stores, oxidative stress, and hepatocellular injury.This preclinical experimental animal study aims to comparatively evaluate the protective effects of N-acetylcysteine (NAC) and silymarin, administered individually and in combination, in an acetaminophen-induced hepatotoxicity model. A total of 40 adult male Sprague Dawley rats will be randomly allocated into five groups (n=8 per group): control, acetaminophen-only, acetaminophen + NAC, acetaminophen + silymarin, and acetaminophen + NAC + silymarin. Hepatotoxicity will be induced by a single oral dose of acetaminophen (1000 mg/kg). NAC and/or silymarin (150 mg/kg each) will be administered orally 2 hours after acetaminophen exposure.Blood samples will be collected at baseline, 2 hours after acetaminophen administration, and at 24 hours prior to sacrifice. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and total bilirubin levels will be analyzed. In addition, liver tissues will be examined histopathologically to assess hepatocellular necrosis and inflammatory changes.The results of this study are expected to provide comparative data on the hepatoprotective efficacy of NAC and silymarin and to evaluate whether combined therapy offers additional benefit over monotherapy in acetaminophen-induced liver injury.