Beltowski_2002_J.Physiol.Pharmacol_53_463

The aim of this study was to investigate the effect of peroxisome proliferator activated receptors alpha agonist, fenofibrate, on the level of oxidative stress, total antioxidant capacity, and plasma paraoxonase 1 (PON 1) activity in the rat. The adult male Wistar rats received fenofibrate for 7 days. The drug was added to food at concentrations 0.005%, 0.05% and 0.5%, which corresponded to doses of 3, 30 and 300 mg/kg/day, respectively. Fenofibrate treatment dose-dependently reduced plasma concentration of malonyldialdehyde and 4-hydroxydialkenals. The level of these lipid peroxidation products in animals treated with 0.005%, 0.05% and 0.5% fenofibrate was lower than in control group by 52.8%, 62.7% and 87.1%, respectively. Lipid hydroperoxides in plasma decreased by 29.7%, 23.4% and 27.5% in these groups, respectively. The drug had no significant effect on total antioxidant capacity measured as ferric reducing ability of plasma (FRAP). Paraoxon-hydrolyzing activity (PON) of plasma paraoxonase was 81.5% lower in animals receiving 0.05% fenofibrate and 69.2% lower in rats treated with 0.5% fenofibrate than in control. Phenyl acetate hydrolyzing activity (arylesterase, AE) was reduced by 15.2%, 49.6% and 55.8% in rats receiving 0.005%, 0.05% and 0.5% fenofibrate, respectively. PON/AE ratio decreased following 0.05% and 0.5% fenofibrate by 64.9% and 30.4%, respectively. The drug had no significant effect on total plasma triglycerides and cholesterol concentrations. The results indicate that fenofibrate treatment favourably modulates oxidant-antioxidant balance and unfavourably affects plasma PON 1 activity in normolipidemic rats. These effects can contribute to the influence of PPARalpha agonists on pathological processes involved in atherogenesis.