COX-2 inhibitors and metabolism of essential fatty acids.
Selective COX-2 inhibitors increase the risk of myocardial infarction and stroke that is attributed to their ability to inhibit prostacyclin (PGI2), lipoxins, resolvins, and endothelial nitric oxide (eNO) but not platelet COX-1 derived thromboxane A2 (TXA2). In contrast, aspirin blocks both COX-1 and COX-2 enzymes that, in turn, increases intracellular concentrations of dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and reduced formation of eicosanoids. On the other hand, such an increase is much less with specific COX-2 inhibitors since they do not block the formation of eicosanoids through COX-1 pathway. DGLA, AA and EPA form precursors to PGE1, PGI2, and PGI3 respectively, which are potent vasodilators and platelet anti-aggregators, and thus aid in the prevention of thrombus formation. EPA has anti-arrhythmic action, and EPA, DHA (docosahexaenoic acid), DGLA, and PGE1 have anti-inflammatory actions as well. EPA, DHA, and AA augment eNO formation that has anti-atherosclerotic action. Hence, combining EFAs with COX-2 inhibitors will prevent thrombotic cardiovascular events.
Das
Undurti N
UN
UND Life Sciences, Cleveland Heights, OH 44106, USA. undurti@hotmail.com
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D015777:Eicosanoids / Q000096:biosynthesis; D011464:Epoprostenol / Q000037:antagonists & inhibitors / Q000378:metabolism; D005228:Fatty Acids, Essential / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D005228:Fatty Acids, Essential; D008565:Membrane Proteins; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin