The endocrine disruptor nonylphenol preferentially blocks cyclooxygenase-1.
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.
Fujimoto
Yohko
Y
Department of Hygienic Chemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan. fujimoto@gly.oups.ac.jp
Sakuma
Satoru
S
Inoue
Tomoe
T
Uno
Eriko
E
Fujita
Tadashi
T
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases; D012756:Sheep
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D010636:Phenols; C025256:nonylphenol; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases