ROLE OF DETOXICATION PATHWAYS IN ACUTE TOXICITY LEVELS OF PHOSPHOROTHIONATE INSECTICIDES IN THE RAT
ROLE OF DETOXICATION PATHWAYS IN ACUTE TOXICITY LEVELS OF PHOSPHOROTHIONATE INSECTICIDES IN THE RAT
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DOI：
10.1016/0024-3205(94)00515-x
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发表时间：
1994-01-01
期刊：
影响因子：
6.1
通讯作者：
CHAMBERS, HW
中科院分区：
文献类型：
--
作者：
CHAMBERS, JE;MA, TG;CHAMBERS, HW
硫代磷酸酯杀虫剂及其活性氧磷代谢物可以通过多种肝脏机制解毒。细胞色素P450介导的脱芳基化活性在男性高于女性。苯巴比妥可诱导两种性别动物的脱芳基化，而β-萘醌仅可诱导雌性动物的脱芳基化。解毒oxons在EDTA的存在下，诱导苯巴比妥，是男性高于女性，和naphthalialesterase活性。在体外钙++依赖性A-酯酶介导的水解毒死蜱-氧磷，但不是对氧磷发生在生物相关的nM浓度。这种水解也可被苯巴比妥诱导。谷胱甘肽介导的共轭似乎没有相关的硫代磷酸酯的处置研究在这里。通过脱芳基化、脂肪酯酶磷酸化和A-酯酶介导的水解（对于某些有机磷酸酯）进行的肝脏解毒似乎都是急性毒性减弱的相关反应。
Phosphorothionate insecticides and their active oxon metabolites can be detoxified by a variety of hepatic mechanisms. Cytochrome P450-mediated dearylation activity was higher in males than in females. While dearylation was induced by phenobarbital in both sexes, it was induced by beta-naphthoflavone in females only. Detoxication of oxons in the presence of EDTA was inducible by phenobarbital, was higher in males than in females, and paralleled aliesterase activity. In vitro Ca++-dependent A-esterase-mediated hydrolysis of chlorpyrifos-oxon but not of paraoxon occurred at biologically relevant nM concentrations. This hydrolysis was also inducible by phenobarbital. Glutathione-mediated conjugation did not appear to be relevant to the disposition of the phosphorothionates studied here. Hepatic detoxication via dearylation, aliesterase phosphorylation and A-esterase-mediated hydrolysis (for some organophosphates) all appear to be relevant reactions in the attenuation of acute toxicity.