Induction of diphenytriazol on cytochrome CYP1A
Abstract
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 alpha-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 alpha-naphthoflavone inhibited the metabolism of phenacetin significantly, and the inhibition constants (K(i)) were (5.4+/-1.0) micromol/L and (10.4+/-0.5) micromol/L, respectively. The activity of microsomes pretreated with diphenytriazol for 4 d was similar to that in b-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.
Keywords:
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 alpha-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 alpha-naphthoflavone inhibited the metabolism of phenacetin significantly, and the inhibition constants (K(i)) were (5.4+/-1.0) micromol/L and (10.4+/-0.5) micromol/L, respectively. The activity of microsomes pretreated with diphenytriazol for 4 d was similar to that in b-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.