Effects of the peroxisome proliferators ciprofibrate and perfluorodecanoic acid on hepatic cellular antioxidants and lipid peroxidation in rats.

The purpose of this study was to determine if hepatic cellular antioxidants and indices of oxidative damage are altered by administration of the peroxisome proliferators ciprofibrate and perfluorodecanoic acid (PFDA). Rats were fed 0.01% ciprofibrate in the diet or were injected with PFDA (0.5 or 5.0 mg/kg, i.p.) every 4 weeks for 6, 14, 30, 54, and 78 weeks. Peroxisomal fatty acyl-CoA oxidase and catalase activities were increased by both ciprofibrate and PFDA throughout the study. Neither ciprofibrate nor PFDA increased the levels of malonaldehyde or conjugated dienes, but ciprofibrate decreased these indices at early time points. Ciprofibrate decreased the following cellular antioxidants or antioxidant enzymes: vitamin C, vitamin D, DT-diaphorase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase; superoxide dismutase and glutathione were not affected. PFDA decreased DT-diaphorase and increased superoxide dismutase, but did not affect other cellular antioxidants. This study shows that administration of the peroxisome proliferators ciprofibrate and PFDA did not increase indices of lipid peroxidation, but that cellular antioxidant defenses were inhibited for a prolonged period of time by the peroxisome proliferator ciprofibrate.