Reduction in human neutrophil superoxide anion generation by n-3 polyunsaturated fatty acids: role of cyclooxygenase products and endothelium-derived relaxing factor.
Dietary supplementation with n-3 polyunsaturated acids (PUFAs) results in augumented vasorelaxation and reduction in superoxide anion generation. Augmented vasorelaxation may be mediated by enhanced generation of vasodilator prostaglandins and/or endothelium-derived relaxing factor (EDRF), now thought to be nitric oxide (NO). To determine the importance of enhanced vasodilator prostaglandins or EDRF-NO in reduction in superoxide anion generation during n-3 PUFAs intake, human polymorphonuclear leukocytes (PMNs) were incubated with n-6 PUFA arachidonic acid (AA), or n-3 PUFAs eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (each 10(-7) M) for 1 hr at 37 degrees C. Parallel sets of PMNs were treated with the cyclooxygenase inhibitors indomethacin (10(-5) M), or aspirin (10(-5) M), or the EDRF-NO synthase inhibitor L-NMMA (10(-3) M) prior to incubation with PUFAs. Superoxide anion generation by PMNs was determined by measuring the superoxide dismutase (SOD) inhibitable reduction of ferricytochrome C. PMNs incubated with EPA or DHA, but not AA, demonstrated marked reduction in superoxide anion generation. This reduction in superoxide anion generation by n-3 PUFAs was abolished by treatment of PMNs with indomethacin or aspirin, but not by L-NMMA. These observations suggest that n-3 PUFAs decrease superoxide anion generation primarily by a prostaglandin-dependent pathway.
Chen
L Y
LY
Department of Medicine, College of Medicine, University of Florida, Gainsville 32610-0277.
Lawson
D L
DL
Mehta
J L
JL
D016718:Arachidonic Acid / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D003864:Depression, Chemical; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000502:physiology; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism*; D019323:omega-N-Methylarginine
D015525:Fatty Acids, Omega-3; D011453:Prostaglandins; D013481:Superoxides; D004281:Docosahexaenoic Acids; D019323:omega-N-Methylarginine; D016718:Arachidonic Acid; D009569:Nitric Oxide; D001120:Arginine; D015118:Eicosapentaenoic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D007213:Indomethacin