Co-administration of fresh grape fruit juice (GFJ) and bergamottin prevented paracetamol induced hepatotoxicity after paracetamol overdose in rats

The aim of this study was to evaluate small doses of known cytochrome P450 enzyme inhibitors, grapefruit juice (GFJ) and one of its components, bergamottin (BGT), for the prevention of paracetamol (PAR)-induced hepatotoxicity after overdose in rats. Six groups of 15 Sprague Dawley (SD) rats each were treated with single oral doses of either saline, PAR only 1725 mg/kg, PAR + GFJ low dose (2 ml) and PAR + GFJ high dose (3 ml), PAR + BGT 0.05 mg/kg (BGT-low) and PAR + BGT 0.22 mg/kg (BGT-high). Thereafter, 5 rats from each group were sacrificed after 24, 48 and 72 h and, on each occasion, blood samples were collected for determination of liver and renal function, full blood count (FBC) and PAR concentration. A piece of liver was sent for histopathology. By 48 h the liver enzymes in the PAR-only group were significantly (P < 0.05) higher than in the PAR + GFJ and PAR + BGT groups, i.e., alanine transaminase (ALT) 837 ± 268 u/L and aspertate transaminase (AST) 1359 ± 405 for PAR only; versus ALT 34 ± 48.8 u/L and AST 238 ± 221 for PAR + GFJ-high; ALT 22 ± 13.9 and AST168 ± 49.6 for PAR + BGT-high; and ALT 52 ± 7.2 u/L and AST 147 ± 153 for the control group. The results correlated with the histopathology findings where livers of the PAR-only group exhibited severe centrilobular and hepatocyte necrosis. In conclusion, GFJ and BGT prevented PAR-induced hepatotoxicity after PAR overdose in rats, and this calls for appropriate observation studies in humans.