Effect of long term, non cholesterol lowering dose of fluvastatin treatment on oxidative stress in brain and peripheral tissues of streptozotocin-diabetic rats

• Published in: European journal of pharmacology Vol. 654; no. 1; pp. 80 - 85
• Main Authors: Cumaoğlu, Ahmet, Ozansoy, Gülgun, Irat, Ali Murat, Arıcıoğlu, Aysel, Karasu, Çimen, Arı, Nuray
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01-03-2011; Elsevier
• Subjects: Administration, Oral; adults; advanced oxidation protein products; Animals; anti-inflammatory activity; antioxidant activity; antioxidants; Antioxidants - administration & dosage; Antioxidants - pharmacology; Biological and medical sciences; biomarkers; Biomarkers - metabolism; brain; Brain - metabolism; catalase; cholesteremic effect; cholesterol; Diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; diabetic complications; drugs; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Acids, Monounsaturated - administration & dosage; Fatty Acids, Monounsaturated - pharmacology; heart; homeostasis; hyperglycemia; hyperlipidemia; Indoles - administration & dosage; Indoles - pharmacology; kidneys; lipid peroxidation; liver; long term effects; Male; malondialdehyde; Medical sciences; nervous system diseases; nitrogen; oxidation; Oxidative stress; Oxidative Stress - drug effects; oxygen; pancreas; Pharmacology. Drug treatments; Rat; Rats; Rats, Wistar; Statin; Streptozocin; Streptozotocin; superoxide dismutase; therapeutics; Oxidative stress; Diabetes; Statin; Rat; Streptozotocin; Endocrinopathy; Antineoplastic agent; Central nervous system; Hypocholesterolemic agent; Encephalon; Fluvastatin; HMG-CoA reductase inhibitor; Enzyme; Diabetes mellitus; Rodentia; Enzyme inhibitor; Statin derivative; Long term; Vertebrata; Antibiotic; Mammalia; Treatment; Animal; Hydroxymethylglutaryl-CoA reductase; Oxidoreductases; Antilipemic agent
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.11.035

One of the main goals of treatment of diabetes mellitus is to prevent its complications. Oxidative stress is universal in diabetes, being ultimately involved with the development complications. As a result of hyperglycemia, reactive oxygen/nitrogen species are produced in various tissues that leads to tissue damage with lipid peroxidation and protein oxidation, along with disruption in cellular homeostasis and accumulation of damaged molecules. Hence, supplementation with antioxidant compounds may offer some protection against diabetic complications. The pleiotropic effects of statins, including antioxidant and anti-inflammatory properties, represent an area of great interest in prevention and therapy of cardiovascular and neurological disorders. Using biomarkers of oxidative stress, in this study we examined the effect of non cholesterol lowering dose, long term fluvastatin treatment on oxidative stress in streptozotocin-diabetic rats. Experiments were conducted in 24 Wistar adult male rats. Diabetic and non-diabetic rats were treated orally for 6months with fluvastatin (2mg/kg/day, p.o) starting one week after streptozotocin injection (55mg/kg, i.p.), (preventive study). In brain, heart, liver, pancreas and kidney homogenates malondialdehyde, lipid hydroperoxide, protein carbonyl content, advanced oxidation protein products, 3-nitrotyrosine levels and superoxide dismutase, catalase activities were measured. Hyperglycemia and dyslipidemia in diabetic groups remained unchanged after fluvastatin treatment. The drug act as antioxidant in the tissues. Hence, antioxidant property of fluvastatin, independent of cholesterol lowering effect, may play a role in prevention of diabetic complications. Clinical relevance of this effect of fluvastatin seems worthy of further studies.