Induction of cyclooxyoenase-H by the peroxisome prohferator ciprofibrate in rats

Many hypolipidemic agents, plasticizers, and industrial pollutants induce peroxisome proliferation in rodents. Many of these peroxisome proliferators have promoting activity in rodent models. Many tumor promoters increase eicosanoid production, yet eicosanoid concentrations are reduced by the peroxisome proliferator ciprofibrate in the liver and in hepatocyte cultures. Peroxisome proliferators have been found to increase the catabolism of eicosanoids, but their effect on eicosanoid synthesis is not known. Cyclooxygenase (COX) is the ratelimiting enzyme of eicosanoid synthesis. Cyclooxygenase consists of two isozymes: COX-I and COX-II. COX-I is generally considered to be a housekeeping enzyme and it is not inducible, whereas COX-II is inducible. In this study, rats were fed 0.01% ciprofibrate in the diet for 10 days, and liver homogenates and microsomes were used for Western blot and enzyme assays. COX-II protein was clearly found to be induced by CIP by Western analysis. These results reveal that ciprofibrate induces COX-II in rat liver.