Effects of endocrine disruptors on arachidonic acid metabolism in rabbit platelets.
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.
Fujimoto
Yohko
Y
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Japan. fujimoto@gly.oups.ac.jp
Sakuma
Satoru
S
Nishiwaki
Yumiko
Y
Ikeda
Mai
M
Fujita
Tadashi
T
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004703:Endocrine System / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D013929:Thromboxane B2 / Q000378:metabolism
D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D011451:Prostaglandin-Endoperoxide Synthases