Induction of diphenytriazol on cytochrome CYP1A

• 来源期刊: 中国药理学报（英文版）
• 学科: 医学
• 关键词: cytochrome P-450 CYP1A diphenytriazol phenacetin liver microsomes metabolism
• 年，卷（期）: 2004,（4）
• 页码范围: 528-533
• 页数: 6页
• 分类号: R9
• 语种: 英文

摘要

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 α-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 α-naphthofiavone inhibited the metabolism of phenacetin significantly, and the inhibition constants (Ki) were (5.4± 1.0) μmol/L and (10.4±0.5)μmol/L, respectively. The activity of microsomes pretreated with diphenytriazol for 4 d was similar to that in β-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.