Dose-Dependent Histopathological and Biochemical Hepatotoxicity of Paracetamol in Rats

Objective: Paracetamol (acetaminophen), a widely used analgesic and antipyretic, poses hepatotoxic risks at overdose due to reactive metabolite (NAPQI) accumulation, glutathione depletion, and oxidative stress. This study investigated the dose-dependent histological effects of paracetamol on rat livers to evaluate subacute (14-day) hepatotoxic effects. Methods: Thirty adult male Wistar rats were randomly assigned to control, low-dose (200 mg/kg/day), and high-dose (500 mg/kg/day) paracetamol groups. These doses were administered orally for 14 days. Liver tissues were processed for histopathological examination by hematoxylin-eosin staining, and lesions were semi-quantitatively scored (0 = none, 3 = severe) for necrosis, congestion, inflammation, vacuolization, and fatty changes. Results: Liver biopsy showed dose-dependent liver injury. Compared to controls, the high-dose group showed marked hepatocellular necrosis (2.8 ± 0.6), sinusoidal congestion (2.5 ± 0.5), inflammatory infiltration (2.7 ± 0.6), vacuolization (2.0 ± 0.4), and fatty changes (1.5 ± 0.3) (p < 0.01). Low-dose rats exhibited less severe changes. The biochemical markers showed significant increases of alanine aminotransferase (ALT) (245.6 ± 32.7 U/L), aspartate aminotransferase (AST) (280.4 ± 40.5 U/L), alkaline phosphatase (ALP) (320.8 ± 35.9 U/L), and bilirubin (2.8 ± 0.6 mg/dL) in the high-dose group compared with the low-dose and control groups (p < 0.01). Conclusion: Prolonged paracetamol administration induces hepatotoxicity, inflammation, and vacuolization in rat livers, with severity correlating to dose. Elevated liver enzymes confirm structural damage, underpinning the dangers of overdose and long-term use.