Hydrogen peroxide metabolism during peroxisome proliferation induced by fenofibrate

LORES ARNAIZ, S.; TRAVACIO, M. ; BOVERIS, A.

Dijon

Congreso; FEBS Satellite International Meeting: Cellular Aspects related to peroxisomes; 1993

FEBS

Peroxisomes proliferators have been suggested to induce liver carcinogenesis as a result of increased peroxisomal H2O2 production.In this study, the hypolipidemic fenofibrate was given to mice (0.23% in the diet) during 1-3 weeks and enzyme activities, H2O2 concentration and chemiluminescence were measured. Maximal effects were found after 15 days of treatment. A 137% increase in liver weight was observed and enzymatic activities of catalase, uricase and glutathione peroxidase were increased by 506%, 58% and 275% respectively in the homogenates. H2O2 steady state concentration showed an increased level in treated mice: 0.15 +/- 0.02 uM as compared with controls (0.09 +/- 0.01 uM). Superoxide dismutase activity was not affected by the treatment. Uricase activity was diminished by 39% in peroxisome-enriched fractions of treated animals. Fenofibrate treatment produced a decrease of 55% both in liver spontaneous chemiluminescence and in hydroperoxide-initiated chemiluminescence, suggesting an increase in the levels of endogenous antioxidants. According to our findings, the imbalance between H2O2 production and its degradation by catalase would result in an increased level of H2O2 steady state concentration during peroxisome proliferation.