Perfluorinated carboxylic acids inhibit cyclooxygenase pathway more potently than 12-lipoxygenase pathway in rat platelets.
Two perfluorinated carboxylic acids (PFCAs), pentadecafluorooctanoic acid (PDFOA) and heptadecafluorononanoic acid (HDFNA), were investigated for potential modulatory effects on the cyclooxygenase (COX) and 12-lipoxygenase (LOX) metabolisms in rat platelets. Both PDFOA and HDFNA dose-dependently inhibited the formation of a COX metabolite, 12-HHT, without any effect on that of a LOX metabolite, 12-HETE, at concentrations ranging from 10 to 100μM. These two PFCAs up to 100μM did not affect platelet membrane integrity, and COX-1 and -2 protein expression levels in Caco-2 cells. These results suggest that PDFOA and HDFNA have the potential to modify platelet function by inhibiting the COX pathway at activity level, but not at protein level.
Sakuma
Satoru
S
Laboratory of Physiological Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. sakuma@gly.oups.ac.jp
Fujii
Yukari
Y
Abe
Muneyuki
M
Arakawa
Yukio
Y
Fujimoto
Yohko
Y
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D018938:Caco-2 Cells; D002210:Caprylates / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats
D002210:Caprylates; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D005466:Fluorocarbons; C008033:12-hydroxy-5,8,10-heptadecatrienoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C023036:perfluorooctanoic acid; C008776:pelargonic acid; D007770:L-Lactate Dehydrogenase; D001092:Arachidonate 12-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases