Induction and inhibition of cytochrome P450 isoforms by imazalil, a food contaminant, in mouse small intestine and liver
Induction and inhibition of cytochrome P450 isoforms by imazalil, a food contaminant, in mouse small intestine and liver
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DOI：
10.1080/004982597239804
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发表时间：
1997-12-01
期刊：
影响因子：
1.8
通讯作者：
Tanaka, K
中科院分区：
文献类型：
--
作者：
Muto, N;Hirai, H;Tanaka, K
1. 研究食品污染物抑霉唑对小鼠小肠粘膜和肝脏细胞色素P450表达和活性的影响。小鼠每天口服抑霉唑1mg/kg或10mg/kg，持续3天。2．在 10 mg/kg/天的剂量水平下，抑霉唑增强了两种组织微粒体中细胞色素 P450 催化的乙氧基试卤灵 O-脱乙基酶和戊氧基试卤灵 O-脱戊酶 (PROD) 活性，表明细胞色素 P450 亚家族 CYP1A 和 CYP2B 的诱导。此外，免疫化学分析还表明，两种组织中CYP2B、CYP2C和CYP3A亚家族的表达均增强。3．在使用小肠和肝微粒体的体外测定中，抑霉唑是细胞色素 P450 依赖性单加氧酶活性（PROD、氨基比林 N-脱甲基酶和红霉素脱甲基酶）的有效抑制剂。4。这些发现表明，抑霉唑不仅具有有效的抑制活性，而且还具有显着的小肠 P450 亚型诱导能力。长时间摄入此类食品污染物可能会调节外源生物进入体循环的主要门户部位的外源代谢酶系统。
1. The effects of imazalil, a food contaminant used as a fungicide, were investigated on the expression and activity of cytochrome P450 in the small intestinal mucosa and liver of mice. Imazalil was orally administered to mice daily at 1 or 10 mg/kg for 3 days.2. Imazalil enhanced cytochrome P450-catalysed ethoxyresorufin O-deethylase and pentoxyresorufin O-depentylase (PROD) activities in both tissue microsomes at the 10 mg/kg/day dose level, indicating the induction of cytochrome P450 subfamilies CYP1A and CYP2B. In addition, immunochemical analyses also demonstrated an enhanced expression of CYP2B, CYP2C and CYP3A subfamilies in both tissues.3. Imazalil was a potent inhibitor of cytochrome P450-dependent monooxygenase activities (PROD, aminopyrine N-demethylase and erythromycin demethylase) in in vitro assays using both small intestinal and liver microsomes.4. From these findings, imazalil has been demonstrated to have not only a potent inhibitory activity but also a significant inducing ability of P450 isoforms in the small intestine. Prolonged ingestion of such a food contaminant may modulate the xenobiotic-metabolizing enzyme system at the site of a primary portal of xenobiotic entry to the systemic circulation.