IBUPROFEN PROTECTS HUMAN ENDOTHELIAL-CELL PROSTAGLANDIN-H SYNTHASE FROM HYDROGEN-PEROXIDE

Human endothelial cells exposed to H2O2 demonstrate decreased prostacy clin (PGI(2)) synthesis due to decreased prostaglandin H synthase (PGH synthase) activity. We tested the hypothesis that PGH synthase activi ty could be protected from H2O2 by a reversible nonsteroidal anti-infl ammatory drug. Experiments demonstrate that ibuprofen, if present duri ng H2O2 exposure, protects endothelial cell PGH synthase against the d ecrease in prostaglandin formation caused by H2O2 Additional studies d emonstrated that decreasing arachidonic acid release from cell phospho lipids during H2O2 exposure did not protect PGI(2) synthesis following H2O2 exposure. In other experiments, ibuprofen did not chelate Fe2+ i n a conformation that inhibited the reactivity of Fe2+. In addition, i buprofen did not scavenge HO .. However, we demonstrate that ibuprofen significantly protects purified PGH synthase cyclooxygenase activity from the effects of H2O2. The results confirm the hypothesis. These fi ndings suggest that ibuprofen displaces oxidant species from the cyclo oxygenase site of PGH synthase, thereby preventing oxidation of the fu nctional groups important for PCH synthase activity.