Effect of methylxanthines on hepatic microsomal enzymes in the rat

Outbred Charles River CD male rats were given one of three methylxanthines (caffeine, theophylline, or theobromine) separately or in combination. Pretreatment with these substances lasted either 3 days, when rats were given high doses of methylxanthines (150 mg/kg/day), or 6 days when the lower doses (37.5 mg/kg/day) were administered. Aniline hydroxylation, p-nitro anisol and aminopyrine demethylation were induced when methylxanthines were given at the high dose (150 mg/kg) but remained unchanged when the lower dose (37.5 mg/kg) was administered. Microsomal enzyme activity was dependent on the length of treatment and on the time of the determination after the last administration. Liver protein synthesis was not influenced by the action of methylxanthines.