羟基化多溴联苯醚(OH-PBDEs)在小鼠肝脏微粒体的体外代谢及对CYP450酶活性的影响In vitro Metabolism and Effects of Hydroxylation Polybrominated Diphenyl Ether( OH-PBDEs) within Mice Hepatic CYP450 Enzymes
张易曦;张圣虎;吴永贵;刘济宁;石利利;
摘要(Abstract):
羟基化多溴联苯醚(OH-PBDEs)是一类具有内分泌干扰效应的酚类化合物,生物毒性要高于母体多溴联苯醚(PBDEs),研究OH-PBDEs的体外代谢行为对于理解其在生物体内的富集转化具有重要意义。以小鼠肝脏微粒体作为研究对象,考察了3-OH-BDE-47、5-OH-BDE-47、6-OH-BDE-47和2’-OH-BDE-68在小鼠肝脏中的体外代谢,并分别研究了浓度为0.1、0.2、0.4、0.6、1.0μmol·L-1条件下4种OH-PBDEs对细胞色素P450酶系中7-乙氧基香豆素-O-脱乙基酶(ECOD)、7-乙氧基异吩唑酮-O-脱乙基酶(EROD)和苯胺4-羟基化酶(ANH)活性的影响。结果表明,4种OH-PBDEs在小鼠肝脏微粒体中均能够快速代谢,代谢率分别为80%(3-OH-BDE-47)、42%(5-OH-BDE-47)、86%(6-OH-BDE-47)和63%(2’-OH-BDE-68)。实验所设OH-PBDEs各浓度对微粒体的ECOD活性无显著性抑制作用,但对EROD的活性均表现出相同的显著抑制作用;4种OH-PBDEs表现出不同的ANH活性影响,即3-OH-BDE-47对ANH活性具有抑制作用,5-OH-BDE-47具有诱导作用,而6-OH-BDE-47和2’-OH-BDE-68对ANH活性无显著性影响。
关键词(KeyWords): OH-PBDEs;肝微粒体;体外代谢;CYP450酶活
基金项目(Foundation): 国家自然科学基金(21407055);; 江苏省自然科学基金(BK20140115)
作者(Author): 张易曦;张圣虎;吴永贵;刘济宁;石利利;
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参考文献(References):
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