Potentiation of paracetamol and carbon tetrachloride-induced hepatotoxicity in rodents by the food additive vanillin

The potential of vanillin to potentiate the paracetamol and carbon tetrachl oride (CCl4)-induced hepatotoxicity was investigated in rats. Vanillin when given alone (15 mg/kg, orally), did not modify liver function in rats as t he values of serum enzymes of alkaline phosphatase (ALP) and amino-transami nases (AST and ALT) were found similar to those in the normal animals. Howe ver, when given repeatedly before the administration of the subtoxic dose o f paracetamol (500 mg/kg) or CCl4 (1 ml/kg), vanillin caused liver damage, as manifested by the significant increase in the serum levels of hepatic en zymes. When tested for its possible interaction with pentobarbital (75 mg/k g, ip) and strychnine (0.9 mg/kg, ip), it caused reduction in pentobarbital -induced sleep in mice as well as preventing the animals against the lethal effect of strychnine, suggestive of an induction of microsomal drug metabo lizing enzymes. These results indicate that vanillin potentiates the hepato toxic potential of paracetamol and CCl4 in rats probably through an enzyme induction process. (C) 1999 Elsevier Science Ltd. All rights reserved.