Experimental Evaluation of Hepatoprotective Activity of Silymarin Against Paracetamol-Induced Hepatotoxicity in Wistar Rats Using Serum Biochemical Assays (ALT, AST, ALP), Oxidative Stress Markers (MDA, SOD, Catalase), and Histopathological Analysis

Abstract

The liver is a vital organ responsible for numerous physiological functions, including metabolism,
detoxification, protein synthesis, and maintenance of biochemical homeostasis. Drug-induced liver
injury remains a significant clinical concern worldwide, with paracetamol overdose being one of
the most common causes of acute hepatic failure. The present study was undertaken to evaluate the
hepatoprotective activity of silymarin against paracetamol-induced hepatotoxicity in Wistar rats
using biochemical, antioxidant, and histopathological parameters. Thirty healthy Wistar rats were
randomly divided into five groups comprising normal control, toxic control, low-dose silymarin-
treated, high-dose silymarin-treated, and standard control groups. Hepatotoxicity was induced by
oral administration of paracetamol (2 g/kg body weight), while silymarin was administered at doses
of 100 mg/kg and 200 mg/kg body weight for seven consecutive days.
Serum biochemical parameters, including alanine aminotransferase (ALT), aspartate
aminotransferase (AST), and alkaline phosphatase (ALP), were estimated to assess liver function.
Oxidative stress was evaluated by measuring malondialdehyde (MDA), superoxide dismutase
(SOD), and catalase levels in liver tissue homogenates. Histopathological examination of liver
sections stained with hematoxylin and eosin was performed to assess structural alterations.
Paracetamol administration resulted in significant elevation of serum ALT, AST, ALP, and MDA
levels, accompanied by marked reductions in SOD and catalase activities, indicating severe hepatic
damage and oxidative stress. Histopathological analysis revealed extensive hepatocellular
degeneration, necrosis, inflammatory infiltration, and disruption of normal hepatic architecture in
the toxic control group. Treatment with silymarin significantly attenuated these alterations in a
dose-dependent manner. Silymarin-treated groups exhibited substantial reductions in serum liver
enzyme levels and lipid peroxidation, along with restoration of antioxidant enzyme activities.
Histological findings demonstrated marked improvement in hepatic architecture, reduced necrosis,
and decreased inflammatory changes compared with the toxic control group. The high-dose
silymarin group showed near-normal biochemical and histological characteristics.
The findings of this study demonstrate that silymarin possesses significant hepatoprotective activity
against paracetamol-induced liver injury, primarily through its antioxidant, membrane-stabilizing,
and tissue-regenerative properties. These results support the therapeutic potential of silymarin as an
effective natural hepatoprotective agent for the management of drug-induced liver disorders.