Caffeine administration enhances acetaminophen-induced hepatic glutathione depletion lipid peroxidation in rats

ABSTRACT

The time course of caffeine-induced depletion of hepatic glutathione and the influence of caffeine on the basal lipid peroxidation state of the liver were examined in rats. These parameters were also evaluated in caffeine-pretreated rats after challenge with acetaminophen. Following a dose of 200 mg/kg of caffeine, the hepatic glutathione content was significantly depleted to 61 and 47% of the value at 0 time, after 2 and 4 hours, respectively. An almost complete recovery of hepatic glutathione was evident at 16 hours after caffeine administration. During this period of time, no significant rise in lipid peroxidation was observed. Subsequent studies with caffeine and acetaminophen showed that the livers of the rats injected with acetaminophen after pretreatment with caffeine exhibited greater glutathione depletion and lipid peroxidation than did the livers of the rats of the other experimental groups. Since hepatic glutathione depletion and lipid peroxidation are important events in acetaminophen induced hepatotoxicity, the present results suggest that the intake of a large amount of caffeine should be considered cautiously during acetaminophen administration