title: Fenofibrate treatment enhances antioxidant status and attenuates endothelial dysfunction in streptozotocin-induced diabetic rats.
abstract: Diabetic endothelial dysfunction is accompanied by increased oxidative stress and upregulated proinflammatory and inflammatory mediators in the vasculature. Activation of peroxisome proliferator-activated receptor-alpha (PPAR-α) results in antioxidant and anti-inflammatory effects. This study was designed to investigate the effect of fenofibrate, a PPAR-α activator, on the endothelial dysfunction, oxidative stress, and inflammation in streptozotocin diabetic rats. Diabetic rats received fenofibrate (150 mg kg(-1) day(-1)) for 4 weeks. Fenofibrate treatment restored the impaired endothelium-dependent relaxation and increased basal nitric oxide availability in diabetic aorta, enhanced erythrocyte/liver superoxide dismutase and catalase levels, ameliorated the abnormal serum/aortic thiobarbituric acid reactive substances, and prevented the increased aortic myeloperoxidase without a significant change in serum total cholesterol and triglyceride levels. It did not affect the decreased total homocysteine level and the increased tumor necrosis factor-α level in the serum of diabetic rats. Fenofibrate-induced prevention of the endothelial function seems to be related to its potential antioxidant and antiinflammatory activity.
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Ege University, Bornova, 35100 İzmir, Turkey. murat.olukman@ege.edu.tr
authors.forename: Murat
authors.initials: M
authors.lastname: Olukman
authors.forename: Ebru Demirel
authors.initials: ED
authors.lastname: Sezer
authors.forename: Sibel
authors.initials: S
authors.lastname: Ulker
authors.forename: Eser Y
authors.initials: EY
authors.lastname: Sözmen
authors.forename: Gülcihan Mehtap
authors.initials: GM
authors.lastname: Cınar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000975:Antioxidants / Q000032:analysis*; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D011345:Fenofibrate / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D000960:Hypolipidemic Agents; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D011345:Fenofibrate