Effects of caffeine on acetaminophen-induced hepatotoxicity and cadmium redistribution in mice

When caffeine (CAF) was given ip to BDF1 mice immediately after an otherwise hepatotoxic dose of acetaminophen (ACM), the hepatotoxic action of ACM was abolished and there was no concomitant redistribution of previously-administered cadmium (Cd) from livers to kidneys as occurred in mice which received ACM only. These observations were not in accord with the recently reported enhancement of ACM hepatotoxicity by CAF following coadministration in rats (Toxicology 34, 95-101, 1985). Conversely, pretreatment of mice with CAF for 3 days followed by ACM injection enhanced the hepatotoxicity of ACM and caused a greater mobilization of Cd from livers to kidneys than was found in mice given ACM alone. The ACM-CAF interaction in mice is thus similar to the ACM-ethanol interaction in rats (Gastroenterology 80, 140-148, 1981; J. Pharmacol. Exptl. Therap. 218, 805-810, 1981). It is proposed that CAF interferes with the metabolism of ACM when administered concomitantly, but induces the microsomal mixed function oxidase system when used in a pretreatment regimen, leading to a more rapid rate of formation of the hepatotoxic arylating ACM biotransformation product.