Cyclooxygenase-2 inhibition improves antioxidative defense during experimental hypercholesterolemia.

摘要

Scientifi c literature shows that in. ammation and oxidative stress contribute in the pathogenesis of atherosclerosis. Th e oxidative stress is the consequence of an imbalance between the free radical generation and elimination. One source of free oxygen radicals is cyclooxygenase (COX) -. and, therefore, inhibiting the activity of this enzyme is likely to reduce oxidative stress. In the present study an experimental rabbit model of hypercholesterolemia was developed and the e. ects of COX-. inhibitors, nimesulide and celecoxib were observed on the activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS). Rabbits were divided into four groups- control, saline, nimesulide and celecoxib, with all groups fed a high cholesterol diet, which only received saline. Low activities of SOD, GPx and TAS were measured in the hypercholesterolemic rabbits pretreated with saline. In the same group, a reciprocal relationship was observed between the LDL-cholesterol concentration and the plasma activities of GPx, SOD and TAS. Rabbits in nimesulide and cele-coxib group showed signifi cantly higher activities of SOD, GPx and TAS in hypercholesterolemic rabbits compared to saline group (p<....). Our study shows that selective and timely use of COX-. inhibitors would be useful in preventing the onset and development of atherosclerosis by enhancing antioxidant defence system