Alteration of enzyme activity in rat liver following the acute and chronic administration of nicotine

Abstract

The ip injection of nicotine (2 or 4 mg/kg) to rats produced an increase in tryptophan pyrrolase activity in liver within 2 hours after drug administration. The elevation in enzyme activity reached a peak at 4 hours after drug injection and returned toward control levels by 6 hours. Administration of 4 mg of nicotine per kilogram to rats 4 times a day for 3 consecutive days produced an elevation of ethylmorphine and norcodeine metabolism in postmitochondrial supernatant fractions from liver. The chronic administration of nicotine (5.9 mg/kg/day) in the drinking water for 7 days produced an elevation in the metabolism of ethylmorphine, norcodeine, and aniline by liver microsomes. This increased enzyme activity was maintained for 5 weeks when nicotine was continued at that dose. However, if the dose was lowered below 4.4 mg/kg/day, the increased activity was not maintained. The activities of tryptophan pyrrolase and tyrosine transaminase were not altered by chronic drug treatment. An increase in the capacity of liver microsomes to synthesize protein was observed when nicotine treatment was continued for 4 weeks. These data indicate (1) that an elevation of microsomal drug-metabolizing enzymes can be achieved after the acute administration of nicotine, but only when convulsive doses are given several times a day, suggesting that the increased activity after acute drug treatment may be a stress-related event; and (2) that the chronic administration of nicotine can increase the activity of drug-metabolizing enzymes, possibly by inducing enzyme synthesis.