Abstract
Background: Oxidative stress induced by hyperglycaemia plays a crucial role in the development of diabetic complications and metformin is commonly used in treating diabetes mellitus (DM). The aim of this study was to investigate whether metformin at the dose of 100 mg/kg/day could ameliorate oxidative stress and improve plasma insulin level in streptozotocin-induced diabetic rats.
Methods: Twenty one rats (8-10 week old; weighing 190-220 g) were assigned into three groups (n=7 rats per group) i.e. non-DM, DM and DM+metformin (100 mg/kg/day metformin) groups. DM was induced using streptozotocin (60 mg/kg) intraperitoneally and treatments were given daily by oral gavage for four weeks. The levels of plasma biomarkers such as fasting blood glucose, oxidant-antioxidant markers and insulin levels were analysed.
Results: Fasting blood glucose, malonyldehyde and protein carbonyls levels were significantly higher while insulin, total antioxidant capacity, catalase and glutathione peroxidase levels were significantly lower in DM group compared to non-DM group. The levels of fasting blood glucose, malonyldehyde and protein carbonyls were significantly lower while levels of total antioxidant capacity, catalase and insulin were significantly higher in DM+metformin group compared to DM group.
Conclusion: This study may suggest that metformin at the dose of 100 mg/kg/day for 4 weeks reduces oxidative stress status and improves plasma insulin level in streptozotocin-induced diabetic rats possibly through its antihyperglycaemic action.
References
American Diabetes Association (ADA, 2014). Classification and Diagnosis of Diabetes. Diabetes Care 2014; 38: S8-S16. http://www.diabetes.org/diabetescare
Geneto M, Umeta M, Kebede T, Azazh A, Nagphaul R, Mohammed SF. Acomparative study on serum level concentration of micrnutrients like zinc, copper and chromium status in type 2 diabetic patients in diabetes and endocrnology unit, Tikur Anbessa specialized Hospital, Ethiopia. J Pharm Nutr Sci 2015; 5: 95-102. http://dx.doi.org/10.6000/1927-5951.2015.05.02.1
Boyle J, Mckey G, Fisher M. Drugs for diabetes: Part 1 metformin. Braz J Cardiol 2010; 17: 231-4.
Hur KY, Lee MS. New mechanisms of metformin action: Focusing on mitochondria and the gut. J Diabetes Investig 2015; 6: 600-9. http://dx.doi.org/10.1111/jdi.12328
Scheen AJ. Clinical pharmacokinetics of metformin. Clin Pharmacokinet 1996; 30: 359-71. http://dx.doi.org/10.2165/00003088-199630050-00003
Gordon EE, Reinking BE, Hu S, et al. Maternal Hyperglycemia directly and rapidly induces cardiac septal overgrowth in Foetal rats. J Diabetes Res 2015; 3: 1-11. http://dx.doi.org/10.1155/2015/479565
Lei XG, Vatamaniuk MZ. Two tales of antioxidant enzymes on beta cells and diabetes. Antioxid Redox Signal 2011; 14(3): 489-503. http://dx.doi.org/10.1089/ars.2010.3416
Anurag P, Anuradha CV. Metformin improves lipid metabolism and attenuates lipid peroxidation in higher fructose-fed rats. J Diab Obes Met 2002; 4: 36-42. http://dx.doi.org/10.1046/j.1463-1326.2002.00178.x
Obi BC, Okoye TC, Okpashi VE, Igwe CN, Alumanah EO. Comparative study of the antioxidant effects of metformin, glibenclamide, and repaglinide in alloxan-induced diabetic rats. J Diab Res 2016; 1: 5-10. http://dx.doi.org/10.1155/2016/1635361
Umar ZU, Abu Bakar AB, Mohamed M. A review on experimental methods of diabetic research: Advantages and limitations. Annu Res Rev Biol 2015; 7: 100-8. http://dx.doi.org/10.9734/ARRB/2015/17404
Trinder P. Determination of blood glucose using an oxidase-peroxidase system with a non-carcinogenichromogen. J Clin Pathol 1969; 22: 158-61. http://dx.doi.org/10.1136/jcp.22.2.158
Janknegt PJ. A comparison of quantitative and qualitative superoxide dismutase assays for application to low temperature microalgae. J Photochem Photobiol B 2007; 87: 218-26. http://dx.doi.org/10.1016/j.jphotobiol.2007.04.002
Zhu T. Effects of the iron-chelating agent deferoxamine on triethylene glycol dimethacrylate, 2-hydroxylethyl methacrylate, hydrogen peroxide-induced cytotoxicity. J Biomed Mater Res B Appl Biomater 2012; 100(1): 197-205. http://dx.doi.org/10.1002/jbm.b.31939-2012-197-205
Pascual P, Martinez-Lara E, Bárcena JA, López-Barea J, Toribio F. Direct assay of glutathione peroxidase activity using high-performance capillary electrophoresis. J Chromatogr 1992; 581: 49-56. http://dx.doi.org/10.1016/0378-4347(92)80446-W
Apak R, Guclu K, Ozyurek M, Karademir SE. Novel total antioxidant capacity index for dietary polyphenols and vitamins C and E, using their cupric ion reducing capability in the presence of neucuproine: CUPRAC method. J Agric Food Chem 2004; 52: 7970-7981. http://dx.doi.org/10.1021/jf048741x-2004-7970-81
Janero DR. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injure. Free Rad Bio Med 1990; 9: 515-40. http://dx.doi.org/10.1016/0891-5849(90)90131-2
Zusterzeel PIM, Mulder TP, Peters WHM. Plasm protein carbonyls nonpregnant healthy pregnant and preeclamptic women. Free Radic Res 2000; 33: 471-76. http://dx.doi.org/10.1080/10715760000301011
Sharifuzzaman SM, Austin B. Kocuria SM1 controls vibriosis in rainbow trout (Oncorhynchus mykiss, Walbaum). J Appl Microbiol 2009; 108: 2162-70. http://dx.doi.org/10.1111/j.1365-2672.2009.04618.x
Cao J, Meng S, Chang E, et al. Low concentrations of metformin suppress glucose production in hepatocytes through AMP-activated protein kinase (AMPK). J Biol Chem 2014; 289: 20435-46. http://dx.doi.org/10.1074/jbc.M114.567271
Bindokas VP, Kuznetsov A, Sreenan S, Polonsky KS, Roe MW, Philipson LH. Visualising superoxide production in normal and diabetic rats islets of Langerhans. J Biol Chem 2003; 278: 9796-801. http://dx.doi.org/10.1074/jbc.M206913200
Del Rio D, Stewart AJ, Pellegrini N. A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. J Nutr Met Cardio Dis 2005; 15: 316-28. http://dx.doi.org/10.1016/j.numecd.2005.05.003
Vilela DD, Peixoto LG, Teixeira RR, et al. The role of metformin in controlling oxidative stress in muscle of diabetic rats. Oxid Med Cel Long 2016; 2016: 1-9. http://dx.doi.org/10.1155/2016/6978625
Kumitoshi U, Katsuya D, Boldbaata D, et al. Lack of TRPM2 impaired insulin secretion and glucose metabolism in mice. J Diabetes 2011; 60: 119-26. http://dx.doi.org/10.2337/db10-0276
Chiswick C, Reynolds RM, Denison F, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2015; 3: 778-86. http://dx.doi.org/10.1016/S2213-8587(15)00219-3
Khan AS, Mcl oughney CR, Ahmed AB. The effect of metform on blood glucose control in overweight patient with type 1 diabetes. J Diabet Med 2006; 23: 1079-84. http://dx.doi.org/10.1111/j.1464-5491.2006.01966.x
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Copyright (c) 2016 Umar Zayyanu Usman, Ainul Bahiyah Abu Bakar , Mahaneem Mohamed