Fujimoto Yohko, Sakuma Satoru, Nishiwaki Yumiko, Ikeda Mai, Fujita Tadashi
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Japan.
Toxicol Appl Pharmacol. 2003 Jun 1;189(2):96-9. doi: 10.1016/s0041-008x(03)00095-4.
To explore the possible actions of endocrine disruptors on the autacoid synthesis in the body, we investigated the effects of nonylphenol (NP), bisphenol A (BPA), di-n-butyl phthalate (DBP), benzyl-n-butyl phthalate (BBP), and di-2-ethylhexyl phthalate (DEHP) on the formation of 12-lipoxygenase metabolite, 12-HETE, and cyclooxygenase metabolites, TXB(2) and 12-HHT, from exogenous arachidonic acid (AA) in rabbit platelets. NP (10-50 microM) showed strong inhibition on the formation of cyclooxygenase metabolites (TXB(2), 34-95% inhibition; 12-HHT, 13-78% inhibition) and weaker inhibition on the formation of 12-HETE (0-49% inhibition). BPA, DBP, BBP, DEHP, and 17beta-estradiol (endogenous estrogen) failed to show any effect on the formation of cyclooxygenase and 12-lipoxygenase metabolites at concentrations up to 100 microM. These results suggest that NP inhibits AA metabolism in platelets and that its effects on the cyclooxygenase pathway predominate over those exerted via the 12-lipoxygenase pathway.
为了探究内分泌干扰物对体内自分泌物质合成的可能作用，我们研究了壬基酚（NP）、双酚A（BPA）、邻苯二甲酸二正丁酯（DBP）、邻苯二甲酸苄基正丁酯（BBP）和邻苯二甲酸二（2-乙基己基）酯（DEHP）对兔血小板中12-脂氧合酶代谢产物12-HETE以及环氧化酶代谢产物TXB₂和12-HHT从外源性花生四烯酸（AA）形成的影响。NP（10 - 50微摩尔）对环氧化酶代谢产物的形成表现出强烈抑制作用（TXB₂，抑制率34 - 95%；12-HHT，抑制率13 - 78%），而对12-HETE形成的抑制作用较弱（抑制率0 - 49%）。BPA、DBP、BBP、DEHP和17β-雌二醇（内源性雌激素）在浓度高达100微摩尔时，对环氧化酶和12-脂氧合酶代谢产物的形成均未显示出任何影响。这些结果表明，NP抑制血小板中的AA代谢，并且其对环氧化酶途径的影响比通过12-脂氧合酶途径产生的影响更为显著。
Zotero 插件