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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Characterization of cytochrome P450 2E1 activity by the (14C)nitrosodimethylamine breath test.
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Characterization of cytochrome P450 2E1 activity by the (14C)nitrosodimethylamine breath test.

机译：通过（14C）亚硝基二甲胺呼气试验表征细胞色素P450 2E1的活性。

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摘要

The objective of this study was to measure the rate of demethylation of nitrosodimethylamine in vivo in the rat and determine its value to assess CYP2E1 activity in intact animals. Nitrosodimethylamine labeled with 14C on both methyl groups was administered to rats and exhaled 14CO2 was collected during 2-3 h. The nitrosodimethylamine breath test was increased by inducers of CYP2E1, such as ethanol (+139%) and 4-methylpyrazole (+115%), and decreased by the inhibitor diallyl sulfide (-53%). In addition, the nitrosodimethylamine breath test was not changed significantly by inducers specific for other cytochrome P450 such as beta-naphthoflavone, dexamethasone, and phenobarbital. The specificity of the induction by 4-methylpyrazole and of the inhibition by diallyl sulfide for CYP2E1 was determined using the [14C]caffeine (CYP1A2), [14C]aminopyrine (CYP2C11), and [14C]erythromycin (CYP3A2) breath tests. 4-Methylpyrazole treatment caused a small increase of the caffeine (+33%) and aminopyrine (+9%) breath tests and no change of the erythromycin breath test. Diallyl sulfide treatment led to a small decrease of the caffeine breath test (-33%) and of the aminopyrine breath test (-13%) but a 23% increase of the erythromycin breath test. It is concluded that the [14C]nitrosodimethylamine breath test is useful to assess CYP2E1 activity in vivo in the rat.
机译：这项研究的目的是测量大鼠体内亚硝基二甲胺的去甲基化速率，并确定其价值以评估完整动物中的CYP2E1活性。将在两个甲基上均标记有14C的亚硝基二甲胺施用于大鼠，并在2-3小时内收集呼出的14CO2。亚硝基二甲胺呼气试验通过CYP2E1的诱导剂增加，例如乙醇（+ 139％）和4-甲基吡唑（+ 115％），而通过抑制剂二烯丙基硫醚（-53％）降低。此外，亚硝基二甲胺呼气试验并未被其他细胞色素P450特异性的诱导剂（如β-萘黄酮，地塞米松和苯巴比妥）显着改变。使用[14C]咖啡因（CYP1A2），[14C]氨基比林（CYP2C11）和[14C]红霉素（CYP3A2）呼气试验确定4-甲基吡唑对CYP2E1的诱导特异性和二烯丙基硫化物对CYP2E1的抑制作用。 4-甲基吡唑治疗导致咖啡因（+ 33％）和氨基比林（+ 9％）呼气试验略有增加，而红霉素呼气试验没有变化。二烯丙基硫醚治疗导致咖啡因呼气试验（-33％）和氨基比林呼气试验（-13％）略有减少，但红霉素呼气试验却增加了23％。结论是，[14C]亚硝基二甲胺呼气试验可用于评估大鼠体内的CYP2E1活性。

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