Fujimoto Yohko, Sakuma Satoru, Inoue Tomoe, Uno Eriko, Fujita Tadashi
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Life Sci. 2002 Mar 29;70(19):2209-14. doi: 10.1016/s0024-3205(01)01538-7.
The anthropogenic chemicals nonylphenol, bisphenol A, phthalic acid benzyl n-butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl) ester have been shown to possess sex hormone-like activity. To explore the possible actions of these chemicals on the autacoid synthesis in the body, we investigated the effects of nonylphenol, bisphenol A, phthalic acid benzyl n-butyl ester, phthalic acid di-n-butyl ester and phthalic acid di(2-ethylhexyl) ester on the activities of cyclooxygenase-1 and -2. Bisphenol A and all three phthalic acid derivatives had no significant effect on the cyclooxygenase-1 and -2 activities up to 100 microM. On the other hand, nonylphenol exhibited a marked inhibition on the cyclooxygenase-1 activity (10-100 microM nonylphenol, 7-95% inhibition), with no detectable change in the activity of cyclooxygenase-2. The inhibition patterns for the substrate, arachidonic acid, and a cofactor, phenol, were competitive and uncompetitive, respectively. These results suggest that nonylphenol can be a selective inhibitor of cyclooxygenase-1 activity.
已证实壬基酚、双酚A、邻苯二甲酸苄基正丁酯、邻苯二甲酸二正丁酯和邻苯二甲酸二（2-乙基己基）酯等人为合成化学物质具有类性激素活性。为探究这些化学物质对体内自分泌物质合成的可能作用，我们研究了壬基酚、双酚A、邻苯二甲酸苄基正丁酯、邻苯二甲酸二正丁酯和邻苯二甲酸二（2-乙基己基）酯对环氧合酶-1和-2活性的影响。双酚A以及所有三种邻苯二甲酸衍生物在浓度高达100微摩尔时对环氧合酶-1和-2的活性均无显著影响。另一方面，壬基酚对环氧合酶-1的活性表现出显著抑制作用（10 - 100微摩尔壬基酚，抑制率为7 - 95%），而环氧合酶-2的活性未检测到变化。对底物花生四烯酸和辅因子苯酚的抑制模式分别为竞争性和非竞争性。这些结果表明壬基酚可能是环氧合酶-1活性的选择性抑制剂。
