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4 References 1. Cicero AF, Tartagni E, Ertek S. Metformin and its clinical use: new insights for an old drug in clinical practice. Arch Med Sci 2012; 8(5): Tavafi M. Complexity of diabetic nephropathy pathogenesis and design of investigations. J Renal Inj Prev 2013; 2(2): Nasri H. Influence of parathyroid hormone on platelet counts and mean platelet volume in hemodialysis. J Parathyr Dis 2014; 2(1): Rafieian-Kopaei M, Baradaran A. Combination of metformin with other antioxidants may increase its renoprotective efficacy. J Renal Inj Prev 2013; 2(2): Detaille D, Guigas B, Chauvin C, Batandier C, Fontaine E, Wiernsperger N, et al. Metformin prevents high-glucose-induced endothelial cell death through a mitochondrial permeability transition-dependent process. Diabetes 2005; 54(7): Rosen P, Wiernsperger NF. Metformin delays the manifestation of diabetes and vascular dysfunction in Goto-Kakizaki rats by reduction of mitochondrial oxidative stress. Diabetes Metab Res Rev 2006; 22(4): Morales AI, Detaille D, Prieto M, Puente A, Briones E, Arevalo M, et al. Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney Int 2010; 77(10): Amini FG, Rafieian-Kopaei M, Nematbakhsh M, Baradaran A, Nasri H. Ameliorative effects of metformin on renal histologic and biochemical alterations of gentamicin-induced renal toxicity in Wistar rats. J Res Med Sci 2012; 17(7): Taheri N, Azarmi Y, Neshat M, Garjani A, Doustar Y. Study the effects of metformin on renal function and structure after unilateral ischemia-reperfusion in rat. Res Pharm Sci 2012; 7(5): S Moussavi MR. Osteoporosis in chronic kidney disease; a mini-review on current knowledge. J Parathyr Dis 2013; 1(1): Sung JY, Choi HC. Metformin-induced AMPactivated protein kinase activation regulates phenylephrine-mediated contraction of rat aorta. Biochem Biophys Res Commun 2012; 421(3): Tavafi M. Protection of renal tubules against gentamicin induced nephrotoxicity. J Renal Inj Prev 2013; 2(1): Rafieian-Kopaei M, Nasri H. Vitamin D therapy in diabetic kidney disease. J Nephropharmacol 2014; 3(1): Nasri H. Impact of diabetes mellitus on parathyroid hormone in hemodialysis patients. J Parathyr Dis 2013; 1(1): Rahimi Z. ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy. J Nephropathol 2012; 1(3): Nasri H, Rafieian-Kopaei M. Metformin improves diabetic kidney disease. J Nephropharmacol 2012; 1(1): Nye HJ, Herrington WG. Metformin: the safest hypoglycaemic agent in chronic kidney disease? Nephron Clin Pract 2011; 118(4): c380-c Spasovski D. Renal markers for assessment of renal tubular and glomerular dysfunction. J Nephropharmacol 2013; 2(2): Papanas N, Maltezos E, Mikhailidis DP. Metformin and heart failure: never say never again. Expert Opin Pharmacother 2012; 13(1): Mojtahedzadeh M, Rouini MR, Kajbaf F, Najafi A, Ansari G, Gholipour A, et al. Advantage of adjunct metformin and insulin therapy in the management of glycemia in critically ill patients. Evidence for nonoccurrence of lactic acidosis and needing to parenteral metformin. Arch Med Sci 2008; 4(2): Nasri H, Rafieian-Kopaei M. Herbal medicine and diabetic kidney disease. J Nephropharmacol 2013; 2(1): Amiri M, Nasri H. Secondary Hyperparathyroidism in chronic kidney disease patients; current knowledge. J Parathyr Dis 2014; 2(1): Kari J. Epidemiology of chronic kidney disease in children. J Nephropathol 2012; 1(3): Baradaran A, Nasri H, Rafieian-Kopaei M. Comment on: Anti-oxidative stress activity of stachys lavandulifolia aqueous extract in humans. Cell J 2013; 15(3): Tavafi M. Diabetic nephropathy and antioxidants. Journal of Nephropathology 2013; 2(1): Ardalan MR, Sanadgol H, Nasri H, Baradaran A, Tamadon MR, Rafieian-Kopaei R. Vitamin D therapy in diabetic kidney disease; current knowledge on a public health problem. J Parathyr Dis 2014; 2(1): Kim J, Shon E, Kim CS, Kim JS. Renal podocyte injury in a rat model of type 2 diabetes is prevented by metformin. Exp Diabetes Res 2012; 2012: Tamadon MR. Secondary hyperparathyroidism and chronic kidney disease. J Parathyr Dis 2013; 1(1): Nayer A, Amyloid A amyloidosis: frequently neglected renal disease in injecting drug users. J Nephropathol 2014; 3(1): !" #$ /307 / 32

5 30. Hajivandi A, Amiri M. World Kidney Day 2014: Kidney disease and elderly. J Parathyr Dis 2014; 2(1): Gobe GC, Morais C, Vesey DA, Johnson DW. Use of high-dose erythropoietin for repair after injury: A comparison of outcomes in heart and kidney. J Nephropathol 2013; 2(3): Baradaran A. Primary hyperparathyroidism and kidney; recent findings. J Parathyr Dis 2014; 2(1): Nasri H. Correlation of serum magnesium with serum levels of 25-hydroxyvitamin D in hemodialysis patients. J Parathyr Dis 2014; 2(1): Hajivandi A, Amiri M. World diabetes day: diabetes mellitus and nephrology. J Nephropharmacol 2013; 2(2): Nasri H, Sahinfard N, Rafieian M, Rafieian S, Shirzad M, Rafieian-kopaei M. Effects of Allium sativum on liver enzymes and atherosclerotic risk factors. J HerbMed Pharmacol 2013; 2(2): Rahimi Z, Mansouri ZO, Rahimi Z, Abbasi A. AT2R G:A polymorphism and diabetic nephropathy in type 2 diabetes mellitus patients. J Renal Inj Prev 2013; 2(3): Nasri H, Motamedi P, Dehghani N, Nasri P, Taheri Z, Kinani F, Torkaman S. Vitamin D and immune system. J Renal Endocrinol 2014; 1: Rafieian-Kopaei M. Medicinal plants for renal injury prevention. J Renal Inj Prev 2013; 2(2): Nasri H. Elevated serum parathyroid hormone is a heart risk factor in hemodialysis patients. J Parathyr Dis 2013; 1(1): Shahbazian H, Rezaii I. Diabetic kidney disease; review of the current knowledge. J Renal Inj Prev 2013; 2(2): Nasri H, Shirzad H. Toxicity and safety of medicinal plants. J HerbMed Plarmacol 2013; 2(2): !"#$ /307 /

6 Journal of Isfahan Medical School Received: Vol. 32, No. 307, 4 th Week, December 2014 Accepted: Abstract Metformin and Renal Protection Mahmoud Rafieian-Kopaei PhD 1, Fatemeh Ghaed-Amini MD 2, Hamid Nasri MD 3 Short Communication Metformin as a biguanid drug entered to the market 50 years ago, and now is generally recommended as the first-line treatment of type 2 diabetes mellitus, especially in overweight patients. However, in recent years,new indications for its use have found. Recently, much attention has been directed toward the possible renal protective efficiency of metformin. Recent studies have proven that metformin, possesses antioxidant efficacy as well. Reduction of apoptosis, induced by oxidative stress in endothelial cells and prevention of vascular dysfunction is found with metformin treatment, too. Keywords: Metformin, Renal protection, Oxidative stress, Antioxidant Citation: Rafieian-Kopaei M, Ghaed-Amini F, Nasri H. Metformin and Renal Protection. J Isfahan Med Sch 2014; 32(307): Professor, Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran 2- General Practitioner, Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran. 3- Professor, Department of Nephrology, School Of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran Corresponding Author: Hamid Nasri MD, hamidnasri@med.mui.ac.ir !" #$ /307 / 32

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