CHEMILUMINESCENCE AND ANTIOXIDANT LEVELS DURING PEROXISOME PROLIFERATION BY FENOFIBRATE

Fenofibrate, the hypolipidemic drug and peroxisome proliferator, was g iven to mice (0.23% w/w in the diet) during 1-3 weeks and H2O2 and TBA RS steady state concentrations, liver chemiluminescence and antioxidan t levels were measured. Administration of fenofibrate during 2 weeks i nduced an increase of 89% in H2O2 steady state concentration. Spontane ous chemiluminescence was decreased by 57% during fenofibrate treatmen t, while no significant effect was observed on TBARS concentration. Hy droperoxide-initiated chemiluminescence was decreased by 56% after 15 days of fenofibrate treatment, probably due to an increase in endogeno us antioxidant levels. Total and oxidized glutathione increased gradua lly after fenofibrate administration, obtaining maximal increases of 6 7% and 58% respectively, after 22 days of treatment. An increase of 55 % was found in ubiquinol levels in treated mice, as compared with the controls. alpha-tocopherol content was decreased by 51% in the liver o f fenofibrate-treated mice. According to our findings, the high rate o f H2O2 production associated with peroxisome proliferation, would not lead to an increase in lipid peroxidation. This can be explained by th e presence of high levels of ubiquinols, which act as an antioxidant. The increased production of H2O2, would lead to DNA damage directly, a nd not through lipid peroxidation processes.