Effects of endocrine disruptors on arachidonic acid metabolism in rabbit platelets

Abstract

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 μM) 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 17β-estradiol (endogenous estrogen) failed to show any effect on the formation of cyclooxygenase and 12-lipoxygenase metabolites at concentrations up to 100 μM. 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.