Increased production of 20‐HETE contributes to the effects of COX inhibitors to prevent the decrease in lipid peroxidation and increase in catalase activity during endotoxemia

Abstract

Increased production of NO and prostanoids associated with a decrease in formation of 20‐HETE contributes to development of hypotension during endotoxemia which is minimized by COX inhibitor indomethacin. NO and prostanoids are known to decrease lipid peroxidation (LP) and increase activity of antioxidant enzymes. We investigated whether 20‐HETE contributes to the effects of COX‐1 and COX‐2 inhibitors on the changes in LP and catalase activity (CA) in endotoxin (ET)‐treated rats. ET‐induced decrease in systemic and renal 20‐HETE levels was associated with a decrease in malonedialdehyde levels and an increase in CA in kidney, heart, aorta or mesenteric artery. These effects of ET were prevented by COX‐1 inhibitor, piroxicam, and COX‐2 inhibitor, NS‐398, or a synthetetic analogue of 20‐HETE, N‐[20‐hydroxyeicosa‐5(Z),14(Z)‐dienoyl]glycine (5,14‐HEDGE). An antagonist of 20‐HETE, 20‐hydroxyeicosa‐6(Z),15(Z)‐dienoic acid, reversed the above effects of 5,14‐HEDGE. These data suggest that an increase in 20‐HETE production contributes to the effects of COX inhibitors to prevent the decrease in LP and increase in CA during endotoxemia. This study was supported by Mersin Univ (2006‐3, B Tunctan), NIH (19134‐33A1, KU Malik; GM31278, JR Falck) and the Robert A Welch Foundation (GL 625910, JR Falck).