title: Short-term gemfibrozil treatment reverses lipid profile and peroxidation but does not alter blood glucose and tissue antioxidant enzymes in chronically diabetic rats.
abstract: In this study, we investigated the efficiency of short-term treatment with gemfibrozil in the reversal of diabetes-induced changes on carbohydrate and lipid metabolism, and antioxidant status of aorta. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.). After 12 weeks of induction of diabetes, the control and diabetic rats were orally gavaged daily with a dosing vehicle alone or with 100 mg/kg of gemfibrozil for 2 weeks. At 14 weeks, there was a significant increase in blood glucose, plasma cholesterol and triglyceride levels of untreated-diabetic animals. Diabetes was associated with a significant increase in thiobarbituric acid reactive substances (TBARS) in both plasma and aortic homogenates, indicating increased lipid peroxidation. Diabetes caused an increase in vascular antioxidant enzyme activity, catalase, indicating existence of excess hydrogen peroxide (H2O2). However, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities in aortas did not significantly change in untreated-diabetic rats. In diabetic plus gemfibrozil group both plasma lipids and lipid peroxides showed a significant recovery. Gemfibrozil treatment had no effect on blood glucose, plasma insulin and vessel antioxidant enzyme activity of diabetic animals. Our findings suggest that the beneficial effect of short-term gemfibrozil treatment in reducing lipid peroxidation in diabetic animals does not depend on a change of glucose metabolism and antioxidant status of aorta, but this may be attributed to its decreasing effect on circulating lipids. The ability of short-term gemfibrozil treatment to recovery of metabolism and peroxidation of lipids may be an effective strategy to minimize increased oxidative stress in diabetic plasma and vasculature.
authors.affiliation: Ankara University, Faculty of Pharmacy, Department of Pharmacology, Tandoğan, Turkey.
authors.forename: G
authors.initials: G
authors.lastname: Ozansoy
authors.forename: B
authors.initials: B
authors.lastname: Akin
authors.forename: F
authors.initials: F
authors.lastname: Aktan
authors.forename: C
authors.initials: C
authors.lastname: Karasu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001011:Aorta / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental; D015248:Gemfibrozil / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D000960:Hypolipidemic Agents; D007328:Insulin; D017392:Thiobarbituric Acid Reactive Substances; D014280:Triglycerides; D002784:Cholesterol; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D015248:Gemfibrozil