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DOI: 10.1055/s-0035-1548822
Ameliorative Effect of Adjunct Therapy of Metformin with Atorvastatin on Streptozotocin-induced Diabetes Mellitus in Rats
Publikationsverlauf
received 07. Februar 2015
accepted 17. März 2015
Publikationsdatum:
08. April 2015 (online)
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Abstract
Metformin has been used for the treatment of diabetes, whereas atorvastatin reduces the incidence of atherosclerosis and ischemic heart disease. Therefore, combined treatment with meformin plus atorvastatin may be beneficial in diabetic patients associated with cardiac disease. The present study was designed to evaluate the combination therapy of metformin and atorvastatin on streptozotocin-induced diabetes mellitus in rats. Blood pressure, serum insulin, glucose, lipid profiles and antioxidant enzymes in pancreatic tissues were measured. Histopathological examination of pancreatic tissues was performed. Streptozotocin treated rats showed significant decrease in body weight and body mass index. Streptozotocin-treated rats showed a significant increase in the levels of blood pressure, serum glucose, triglycerides, total cholesterol and thiobarbituric acid reactive substance as well as a significant decrease in the levels of serum insulin, high density lipoprotein and reduced glutathione in pancreatic tissues. Administration of metformin plus atorvastatin for a period of 14 days significantly improved these biochemical parameters near to normal. The protective effect of metformin plus atorvaststin against streptozotocin-induced diabetes was further confirmed by histopathological examination. The results of present study suggest that metformin plus atorvastatin possess antioxidant activity and has a significant protective effect against streptozotocin-induced diabetes mellitus.
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References
- 1 WHO . Definition diagnosis and classification of diabetes mellitus and its complications. World Health Organization Department of Non-communicable Disease Surveillance. 1999 ( http://whglibdoc.who.int/hg/1999/WHO-NCD-NCS-99.2pdf ) 60 p. Retrieved on 7/6/2012
- 2 Sharma S, Singh M, Sharma PL. Beneficial effect of insulin in hyperhomocysteinemia and diabetes mellitus-induced vascular endothelium dysfunction: role of phosphoinositide dependent kinase and protein kinase B. Molecular and cellular Biochemistry 2011; 348: 21-32
- 3 Farah R, Shurtz-Swirski R, Lapin O. Intensification of oxidative stress and inflammation in type 2 diabetes despite antihyperglycemic treatment. Cardiovascular Diabetologia 2008; 7: 1-8
- 4 Linthout SV, Riad A, Dhayat N et al. Anti-inflammatory effect of atorvastatin improves left ventricular function in experimental diabetic cardiomyopathy. Diabetologia 2007; 50: 1977-1986
- 5 Adler AI, Shaw EJ, Stokes T et al. Newer agents for blood glucose control in type 2 diabetes: summary of NICE guidance. BMJ (Clinical research ed) 2009; 338: 1668
- 6 Nathan DM, Buse JB, Davidson MB et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009; 32: 193-203
- 7 Stafford JM, Elasy T. Treatment update thiazolidinediones in combination with metformin for the treatment of type 2 diabetes. Journal of Vascular Health and Risk Management 2007; 3: 503-510
- 8 Dandona P, Aljada A, Ghanim H et al. Increased Plasma Concentration of Macrophage Migration Inhibitory Factor (MIF) and MIF mRNA in Mononuclear Cells in the Obese and the Suppressive Action of Metformin. Journal of Clinical Endocrinology and Metabolism 2004; 89: 5043-5047
- 9 Anfossi G, Russ I, Bonomo K et al. The cardiovascular effect of metformin: further reasons to consider an old drug a cornerstone in the therapy of type 2 diabetes mellitus. Current Vascular Pharmacology 2010; 8: 327-337
- 10 Srinivas M, Annapurna A, Reddy YN. Anti-atherosclerotic effect of atorvastatin and clopidogrel alone and in combination in rats. Indian Journal of Experimental Biology 2008; 46: 698-703
- 11 Mehany HA, Abo-youssef AM, Ahmed LA et al. Protective effect of vitamin E and atorvastatin against potassium dichromate – induced nephrotoxicity in rats. Journal of Basic and Applied Sciences 2013; 2: 96-102
- 12 Okhawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry 1979; 95: 351-358
- 13 Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82: 70-77
- 14 Kianifard D, Sadrkhanlou R, Hasanzadeh S. The histological, histomorphometrical and histochemical changes of testicular tissue in metformin treated and untreated streptozotocin – induced adult diabetic rats. Vet Res Forum 2011; 2: 13-24
- 15 Juarez-Rojop IE, Díaz-Zagoya JC, Ble-Castilo JL et al. Hypoglycemic effect of Carica papaya leaves in streptozotocin-induced diabetic rats. BMC Complementary and Alternative Medicine 2012; 12: 1-11
- 16 Sharma SB, Nasir A, Prabhu KM et al. Hypoglycaemic and hypolipidemic effect of ethanolic extract of seeds of Eugenia jambolana in alloxan-induced diabetic rabbits. Journal of Ethnopharmacology 2003; 85: 201-206
- 17 Zhang Q, Wang GJ. Application of GC/MSbased metabonomic proling in studying the lipid-regulating effects of Ginkgo biloba extract on diet-induced hyperlipidemia in rats. Acta Pharmacologica Sinica 2009; 30: 1674-1687
- 18 De Sereday MS, Gonzalez C, Giorgini D et al. Prevalence of diabetes, obesity, hypertension and hyperlipidemia in the central area of Argentina. Diabetes and Metabolism 2004; 30: 335-339
- 19 Wang HJ, Jin YX, Shen W et al. Low dose streptozotocin (STZ) combined with high energy intake can effectively induce type 2 diabetes through altering the related gene expression. Asia Pacific Journal of Clinical Nutrition 2007; 16: 412-417
- 20 Tripathi UN, Chandra D. The plant extracts of Momordica charantia and Trigonella foenum graecum have antioxidant and anti-hyperglycemic properties for cardiac tissue during diabetes mellitus. Oxidative Medicine and Cellular Longevity 2009; 2: 290-296
- 21 Ramesh B, Saralakumari D. Antihyperglycemic, hypolipidemic and antioxidant activities of ethanolic extract of Commiphora mukul gum resin in fructose fed male Wistar rats. Journal of Physiology and Biochemistry 2012; 68: 573-582
- 22 Robertson RP, Tanaka Y, Takahashi H et al. Prevention of oxidative stress by adenoviral overexpression of glutathione-related enzymes in pancreatic islets. Annals of the New York Academy of Sciences 2005; 1043: 513-520