Induction of diphenytriazol on cytochrorne CYP1A

AIM: To study the effects of diphenytriazol on cytochrome P-450 (CYP) enzymes. METHODS: SD rats were pretreated with diphenytriazol. The catalytic activities of rat liver microsomes were determined by assaying ethoxyresorufin-O-deethylase (EROD) and pentoxyresorufin-O-dealkylase. Phenacetin and aminopyrine were selected as the substrate of CYP1A and CYP2B, respectively. The concentration of remaining substrate in microsomal incubates was determined by reversed-phase high-performance liquid chromatography (RP-HPLC). The inhibition of fluvoxamine or (x-naphthoflavone on phenacetin metabolism was measured. RESULTS: Phenacetin was significantly metabolized in the diphenytriazol-treated microsomes and the metabolic degree increased according to the diphenytriazol-treatment days. There existed a significant correlation between the metabolic degree of phenacetin and EROD in the microsomes pretreated with diphenytriazol. Both fluvoxamine and a-naphthoflavone inhibited the metabolism of phenacetin significantly, and the inhibition constants (K-i) were (5.4 +/- 1.0) mumol/L and (10.4 +/- 0.5) mumol/L, respectively. The activity of microsomes pretreated with diphenytriazol for 4 d was similar to that in beta-naphthoflavone group, but was significantly different from those in control group and phenobarbital group. CONCLUSION: These results reveal that diphenytriazol is a novel inducer of CYP1A.