Activation of acetaminophen oxidation in rat liver microsomes by caffeine

Addition of caffeine in vitro stimulated the oxidative metabolism of acetaminophen by rat liver microsomes, resulting in increased formation of acetaminophen-glutathione (GSH) conjugates and increased covalent binding of acetaminophen to microsomal protein. This metabolic enhancement by caffeine was most prominent using liver microsomes from phenobarbital (PB)-treated rats. Liver microsomes obtained from rats treated with ethanol-oxidized acetaminophen at much faster rates than microsomes from control, PB-treated or 3-methylcholanthrene (3-MC)-treated animals. The stimulatory effect of caffeine was, however, minimal in liver microsomes obtained from ethanol-treated rats.