CHARACTERIZATION OF THE INDUCTION OF RAT MICROSOMAL CYTOCHROME-P450 BY TACRINE

The effect of multiple dose tacrine (THA) administration at 2 and 20 m g/kg (single oral doses for 2 weeks) on cytochrome P450 (CYP) was exam ined in male and female Wistar rats, Changes in CYP were determined by measuring total spectral CYP, the rates of ethoxy and pentoxyresorufi n dealkylations, and the protein expression of several CYPs by western blot analysis of liver microsomes. Animals treated with beta-naphthof lavone or phenobarbital were employed as positive controls. No physiol ogical or metabolic changes were observed in male or female rats treat ed with 2 mg/kg THA for 2 weeks. Male and female animals treated with 20 mg/kg THA for 2 weeks demonstrated increased CYP1A activity (increa sed ethoxyresorufin deethylase activity) and increased expression of C YP1A1 with only minor increases in CYP1A2 expression. Compared with th e effects of beta-naphthoflavone induction of CYP1A, the induction obs erved with THA at 20 mg/kg was considered minor. (C) 1997 Elsevier Sci ence Inc.