Acetaminophen-induced hepatotoxicity: antagonistic action of caffeine in mice.

Studies of interactions in mice between acetaminophen (ACM) and caffeine (CAF) revealed that CAF given immediately after ACM antagonized the acute toxicity of ACM and reduced the severity of ACM-induced hepatic necrosis as assessed grossly and microscopically. It also attenuated the elevations of SGOT and SGPT levels following ACM administration. CAF reduced significantly the magnitude of ACM-induced mobilization of cadmium from hepatic cadmium-metallothionein stores and the extent of binding of 3H-ACM to hepatic proteins. CAF did not restore hepatic GSH levels toward control values in ACM-treated mice; administration of CAF alone led to a reduction of hepatic GSH concentrations. It was concluded that the antagonistic action by CAF of ACM toxicity in mice is not mediated through a salutary effect on endogenous hepatic sulfhydryl levels. The significance of these observations was discussed in terms of possible interactions at the level of ACM and CAF biotransformation and the potential for interactions of CAF with other xenobiotics.