Induction of liver and kidney CYP1A1/1A2 by caffeine in rat
Induction of liver and kidney CYP1A1/1A2 by caffeine in rat
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DOI：
10.1016/s0006-2952(96)00522-9
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发表时间：
1996-12-24
影响因子：
5.8
通讯作者：
Berthou, F
中科院分区：
文献类型：
--
作者：
Goasduff, T;Dreano, Y;Berthou, F
在实验动物和人类中，通过肝微粒体P450酶的咖啡因代谢得到了很好的证明。然而，其对P450酶的诱导作用尚未得到深入研究。在初步实验中，1 mM咖啡因与大鼠肝细胞培养物的时间依赖性孵育导致其自身代谢率的增加。大鼠肝、肾细胞色素（Cytochromes，CYP）1A 1/1A 2的表达随咖啡因剂量的增加而增加。P450表达采用特异性酶活性和北方印迹分析。咖啡因导致微粒体制剂中肝脏CYP 1A 1/1A 2活性呈剂量依赖性升高，根据50和150 mg咖啡因/kg/天持续3天的给药方案，乙氧基试卤灵O-脱乙基酶和甲氧基试卤灵O-脱甲基酶的升高幅度分别为1.7- 6倍和3 - 8.9倍。北方印迹分析表明，在50-150 mg咖啡因/kg/天的剂量方案下，咖啡因处理分别增加了肝脏CYP 1A 1和CYP 1A 2 mRNA水平，持续3天。本研究结果表明，咖啡因以剂量依赖性方式增加自身代谢，并通过转录激活或mRNA稳定诱导CYP 1A 1/1A 2表达。版权所有（C）1996 Elsevier Science Inc.
Caffeine metabolism by hepatic microsomal P450 enzymes is well documented in experimental animals and humans. However, its induction effect on P450 enzymes has not been thoroughly studied. In a preliminary experiment, the time dependent incubation of 1 mM caffeine with rat hepatocyte culture resulted in an increase of its own metabolic rate. The dose-dependent expression of rat hepatic and renal cytochromes (CYP) 1A1/1A2 was then investigated after per os administration of caffeine. P450 expression was monitored by using specific enzymatic activities and Northern blot analysis. Caffeine caused a dose dependent elevation of hepatic CYP1A1/1A2 activities in microsomal preparations, which ranged from 1.7- to 6-fold for ethoxyresorufin O-deethylase and 3 to 8.9-fold for methoxy resorufin O-demethylase according to the dose regimen of 50 and 150 mg caffeine/kg/day for 3 days, respectively. Northern blot analysis demonstrated that caffeine treatment increased liver CYP1A1 and CYP1A2 mRNA levels over the dose regimen of 50-150 mg caffeine/kg/day for 3 days, respectively. The result of this study demonstrates that caffeine increases its own metabolism in a dose-dependent manner and induces CYP1A1/1A2 expression through either transcriptional activation or mRNA stabilization. Copyright (C) 1996 Elsevier Science Inc.