Pyrazole as a modifier of liver microsomal monooxygenase in DBA/2N and AKR/J mice

Effects of pyrazole on liver microsomal monooxygenase was studied in two inbred strains of mice, DBA/2N (D2) and AKR/J (AKR). A selective effect on microsomal monooxygenase was found. In the D2 mouse pyrazole strongly increases the coumarin 7-hydroxylase (CoH) and 7-ethoxycoumarin O-deethylase (ECDE) activities while on the total cytochrome P-450 (P-450) content and ethylmorphine N-demethylase (EMDM) and benzo(a)pyrene hydroxylase (AHH) activities the effect is biphasic (increased with lower doses and decreased with higher). For AKR the effect of pyrazole is different from the D2. The increase of CoH and ECDE is weaker and no biphasic effect for the other three parameters can be seen. Instead only a decrease takes place. The optimal dose of pyrazole for the induction of CoH in the D2 mice is 200 mg/kg once a day during three days. The effect of pyrazole is strongest in animals (D2) of 4-10 weeks old. For young animals (2 weeks old) no effect except of a weak decrease in AHH can be seen. Also for old animals the effect is weak. Recovery of the monooxygenase after pyrazole induction takes place in about 120 hr except for the total P-450 content which is still below normal. No sex dependence in the effect of pyrazole on CoH was found.