Histopathological Alternation in The Liver of Experimental Rodents Following Hepatotoxic Insults

Abstract

This study adhered to international ethical standards for animal research and investigated acute and sub chronic liver injury in rodents induced by acetaminophen (APAP) or carbon tetrachloride (CCl₄). A total of 120 male rodents (60 Wistar rats, 60 C57BL/6 mice) were divided into eight groups (n=15). Hepatotoxicity was induced via single or repeated intraperitoneal injections (APAP: 300 mg/kg; CCl₄: 2.0 mL/kg), with euthanasia at 12 hours, 24 hours, 72 hours, 7 days, and 28 days. Serum biomarkers (ALT, AST, GLDH, HA, MDA) and histopathology (H&E, Masson’s trichrome, α-SMA) were assessed. Histological scoring (0-4) showed high inter-rater reliability (κ > 0.85). Results revealed early oxidative stress (MDA ↑ at 12 hours), peak necrosis (ALT/GLDH ↑ at 24-72 hours), and bridging fibrosis in CCl₄-treated rats by Day 28 (HA ↑ 7-fold, p < 0.001). APAP caused more severe acute necrosis in mice; CCl₄ induced pronounced fibrogenesis in rats. GLDH strongly correlated with necrosis (r = 0.84), and HA best predicted fibrosis stage (R² = 0.79, p < 0.001).