Abstract

PROTECTIVE IMPACT OF CURCUMIN AGAINST PARACETAMOL-INDUCED HEPATOTOXICITY IN RATS

Abiodun V. Y.*, Okunola O. J., Omueti F. O., Akorede A. O., Usman R. O., Adesile O. C., Owoko S. E. Bankole B. A.

ABSTRACT

Paracetamol overdose remains one of the leading causes of drug-induced liver injury worldwide owing to excessive production of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), oxidative stress, inflammation and hepatocellular necrosis. This study investigated the protective impact of curcumin against paracetamol-induced hepatotoxicity in Wistar rats. Twenty-five healthy adult male Wistar rats were randomly assigned into five groups comprising the control, curcumin only, paracetamol (PCM), curcumin plus paracetamol, and N-acetylcysteine (NAC) plus paracetamol groups. Animals received oral administration of curcumin (400 mg/kg) and NAC (150 mg/kg) for fourteen consecutive days before paracetamol induction. Hepatoprotective activity was assessed using body weight, liver index, liver function biomarkers (ALT, AST, ALP, bilirubin and albumin), oxidative stress biomarkers (MDA, SOD, CAT and GSH), reactive oxygen species, inflammatory cytokines (TNF-α, IL-6 and nitric oxide), DNA fragmentation, caspase-3 activity and histopathological examination. Paracetamol administration significantly reduced body weight while markedly increasing liver index, serum ALT, AST, ALP and bilirubin concentrations. Oxidative stress was evidenced by increased MDA and ROS levels together with depletion of SOD, CAT and GSH activities. Similarly, inflammatory cytokines, DNA fragmentation and caspase-3 activity were significantly elevated, while albumin concentration was reduced. Histopathological examination further revealed severe hepatic necrosis and structural degeneration in the paracetamol-treated rats. Pretreatment with curcumin significantly ameliorated these biochemical and histological abnormalities by reducing liver enzyme activities, oxidative stress, inflammatory mediators and apoptotic indices while restoring antioxidant enzyme activities, serum albumin concentration and normal hepatic architecture. The hepatoprotective efficacy of curcumin was comparable with that of N-acetylcysteine. The findings demonstrate that curcumin possesses potent antioxidant, anti-inflammatory and anti-apoptotic properties capable of protecting against paracetamol-induced liver injury. Curcumin therefore represents a promising natural therapeutic agent for preventing drug-induced hepatotoxicity.

Keywords: Curcumin, Paracetamol, Hepatotoxicity, Oxidative Stress, Antioxidants, Liver Function, Inflammation, Histopathology, Wistar Rats, Hepatoprotection.