Chemiluminescence and antioxidant levels during peroxisome proliferation by fenofibrate

LORES ARNAIZ, S.; TRAVACIO, M.; MONSERRAT, A.J.; CUTRÍN, J.C.; LLESUY, S.; BOVERIS, A.

BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE

ELSEVIER SCIENCE BV

Año: 1997 vol. 1360 p. 222 - 228

0925-4439

Fenofibrate, the hypolipidemic drug and peroxisome proliferator, was given to mice 0.23% wrw in the diet. during 1–3 weeks and H O and TBARS steady state concentrations, liver chemiluminescence and antioxidant levels were measured. Administration of fenofibrate during 2 weeks induced an increase of 89% in H O steady state concentration. Spontaneous chemiluminescence was decreased by 57% during fenofibrate treatment, while no significant effect was observed on TBARS concentration. Hydroperoxide-initiated chemiluminescence was decreased by 56% after 15 days of fenofibrate treatment, probably due to an increase in endogenous antioxidant levels. Total and oxidized glutathione increased gradually after fenofibrate administration, obtaining maximal increases of 67% 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. a-tocopherol content was decreased by 51% in the liver of fenofibrate-treated mice. According to our findings, the high rate of H O production associated with peroxisome proliferation, would not lead to an increase in lipid peroxidation. This can be explained by the presence of high levels of ubiquinols, which act as an antioxidant. The increased production of H O , would lead to DNA damage directly, and not through lipid peroxidation processes.0.23% wrw in the diet. during 1–3 weeks and H O and TBARS steady state concentrations, liver chemiluminescence and antioxidant levels were measured. Administration of fenofibrate during 2 weeks induced an increase of 89% in H O steady state concentration. Spontaneous chemiluminescence was decreased by 57% during fenofibrate treatment, while no significant effect was observed on TBARS concentration. Hydroperoxide-initiated chemiluminescence was decreased by 56% after 15 days of fenofibrate treatment, probably due to an increase in endogenous antioxidant levels. Total and oxidized glutathione increased gradually after fenofibrate administration, obtaining maximal increases of 67% 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. a-tocopherol content was decreased by 51% in the liver of fenofibrate-treated mice. According to our findings, the high rate of H O production associated with peroxisome proliferation, would not lead to an increase in lipid peroxidation. This can be explained by the presence of high levels of ubiquinols, which act as an antioxidant. The increased production of H O , would lead to DNA damage directly, and not through lipid peroxidation processes.