Sl. Arnaiz et al., CHEMILUMINESCENCE AND ANTIOXIDANT LEVELS DURING PEROXISOME PROLIFERATION BY FENOFIBRATE, Biochimica et biophysica acta. Molecular basis of disease, 1360(3), 1997, pp. 222-228
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.