title: The effect of peroxisome proliferator-activated receptors alpha (PPARalpha) agonist, fenofibrate, on lipid peroxidation, total antioxidant capacity, and plasma paraoxonase 1 (PON 1) activity.
abstract: 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.
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase; D004950:Esterases / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008055:Lipids / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014157:Transcription Factors / Q000819:agonists*
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D004950:Esterases; D043303:Aryldialkylphosphatase; D011345:Fenofibrate