Pharmacology and Toxicology Unit, Institute of Biomedicine, University of Oulu, Oulu, Finland.
J Environ Sci Health B. 2009 Aug;44(6):553-63. doi: 10.1080/03601230902997766.
The goal of this work was to study the ability of 18 pesticides to inhibit selective model activities for all major xenobiotic-metabolizing enzymes, namely CYP1A1/2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. Generally organophosphorus insecticides were the most potent and extensive inhibitors, especially towards CYP1A1/2 (IC(50) values of chlorpyrifos, fenitrothion and profenofos approximately 3 micro M), CYP2B6 (IC(50) values of chlorpyrifos and fenitrothion 2.5 micro M), CYP2C8 (fenitrothion 4.3 micro M), CYP2C9 (fenitrothion and malathion 4.8 and 2.5 micro M, respectively), CYP2D6 (chlorpyrifos and phenthoate approximately 3 micro M) and CYP3A4 (chlorpyrifos, fenitrothion and phenthoate 3-4 micro M). Otherwise there were quite considerable differences in potency and extent of inhibition between different organophosphates. Pyrethroids were in general very weak or inactive. Deltamethrin and fenvalerate were potent inhibitors of CYP2D6 (IC(50) values of approximately 3 micro M) while lambda-cyhalothrin potently inhibited both CYP2D6 and CYP3A4-mediated activities (IC(50)'s about 3-4 micro M). Some pesticides caused relatively potent inhibitions sporadically (carbendazim, CYP2D6, IC(50) = 12 micro M; atrazine, CYP3A4, IC(50) = 2.8 micro M; glyphosate, CYP2C9, IC(50) = 3.7 micro M; hexaflumuron, IC(50) = 6.0 micro M). With the exceptions of alpha-cypermethrin, cypermethrin, isoproturon, carbaryl and abamectin, most pesticides inhibited relatively potently at least one CYP-selective activity, which may have relevance for potential interactions in occupational exposures and for further studies on the CYP-associated metabolism of respective pesticides.
本研究旨在考察 18 种农药对主要的异生物质代谢酶（包括 CYP1A1/2、2A6、2B6、2C8、2C9、2C19、2D6、2E1 和 3A4）的选择性模型活性的抑制能力。一般来说，有机磷杀虫剂是最有效和广泛的抑制剂，尤其是对 CYP1A1/2（毒死蜱、fenitrothion 和 profenofos 的 IC50 值约为 3μM）、CYP2B6（毒死蜱和 fenitrothion 的 IC50 值为 2.5μM）、CYP2C8（fenitrothion 的 IC50 值为 4.3μM）、CYP2C9（fenitrothion 和 malathion 的 IC50 值分别为 4.8μM 和 2.5μM）、CYP2D6（毒死蜱和 phenthoate 的 IC50 值约为 3μM）和 CYP3A4（毒死蜱、fenitrothion 和 phenthoate 的 IC50 值为 3-4μM）。此外，不同有机磷杀虫剂之间的抑制能力和抑制程度存在较大差异。拟除虫菊酯类一般较弱或无活性。除虫菊酯和 fenvalerate 是 CYP2D6 的有效抑制剂（IC50 值约为 3μM），而 lambda-cyhalothrin 则能有效抑制 CYP2D6 和 CYP3A4 介导的活性（IC50 值约为 3-4μM）。有些农药偶尔会引起相对较强的抑制作用（carbendazim，CYP2D6，IC50=12μM；atrazine，CYP3A4，IC50=2.8μM；glyphosate，CYP2C9，IC50=3.7μM；hexaflumuron，IC50=6.0μM）。除了 alpha-cypermethrin、cypermethrin、isoproturon、carbaryl 和 abamectin 外，大多数农药至少对一种 CYP 选择性活性具有较强的抑制作用，这可能与职业暴露中的潜在相互作用以及对各自农药的 CYP 相关代谢的进一步研究有关。
