Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients Arpita Chakraborty a , Subhankar Chowdhury b , Maitree Bhattacharyya a, * a Department of Biochemistry, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, India b Institute of Postgraduate Medical Education and Research, Government of West Bengal, 224, Acharyya Jagadish Chandra Bose Road, Kolkata 700020, India 1. Introduction Type 2 diabetes is a multifactorial metabolic disorder charac- terized by abnormal insulin secretion caused by impaired b cell function and insulin resistance in target tissues [1,2]. India leads global top 10 in terms of the highest number of people with diabetes mellitus, though very few clinical studies have been performed on Indian diabetic population. Despite significant recent advances in hyperglycemia, real cure of type 2 diabetes is still beyond the horizon. Different oral hypoglycemic drugs are being used nowadays among which metformin (Biguanide family) has greatly improved the prognosis of diabetic patients by improving insulin sensitivity and protecting against vascular complication, especially for the patients accompanied with obesity and insulin resistance. Oxidative stress and inflammation resulting tissue damage are hallmarks of chronic diseases like diabetes. Increased production and/or ineffective scavenging of reactive oxygen species (ROS), advanced oxidation protein product (AOPP) and accumulation of advanced glycation end products (AGE) play crucial role in diabetes pathogenesis. Nitric oxide (NO), an inorganic molecule formed by vascular endothelial cells is now thought to be a messenger molecule that also plays a significant role in various biological processes. Mg +2 and Ca +2 are important diabetes research and clinical practice xxx (2010) xxx–xxx article info Article history: Received 16 September 2010 Received in revised form 11 November 2010 Accepted 18 November 2010 Keywords: Oxidative stress Nitrosative stress Inflammation Metformin abstract Aim: Advanced research has radically changed both diagnosis and treatment of diabetes during last three decades; a number of classes of oral antidiabetic agents are currently available for better glycemic control. Present study aims to evaluate the effect of metformin on different stress and inflammatory parameters in diabetic subjects. Methods: 208 type 2 diabetes patients were randomly assigned for metformin and placebo. Results: Reactive oxygen species generation, advanced oxidation protein products (179.65  13.6, 120.65  10.5 mmol/l) and pentosidine (107  10.4, 78  7.6 pmol/ml) were found to be reduced by metformin treatment compared to placebo. On the other hand metformin administration enhanced total thiol and nitric oxide level ( p < 0.05). But nutrient level (Mg +2 , Ca +2 ) in plasma was not altered by the treatment. Significant restoration of C reactive protein ( p < 0.05) was noticed after metformin therapy. Metformin administration also improved Na + K + ATPase activity (0.28  0.08, 0.41  0.07 mmol Pi/mg/h) in erythrocyte membrane. Conclusions: This study explores that metformin treatment restores the antioxidant status, enzymatic activity and inflammatory parameters in type 2 diabetic patients. Metformin therapy improves the status of oxidative and nitrosative stress altered in type 2 diabetes. This study unfolds the cardio protective role of metformin as an oral hypoglycemic agent. # 2010 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +91 33 24614712; fax: +91 33 24614849. E-mail addresses: bmaitree@gmail.com, bmaitree@sify.com (M. Bhattacharyya). Abbreviations: AOPP, advanced oxidation protein products; CRP, C reactive protein; NO, nitric oxide; NOS, nitric oxide synthase; OHAs, oral hypoglycemic agents. DIAB-4984; No. of Pages 7 Please cite this article in press as: Chakraborty A, et al. Effect of metformin on oxidative stress, nitrosative stress and inflammatory biomarkers in type 2 diabetes patients. Diab Res Clin Pract (2010), doi:10.1016/j.diabres.2010.11.030 Contents lists available at ScienceDirect Diabetes Research and Clinical Practice journal homepage: www.elsevier.com/locate/diabres 0168-8227/$ – see front matter # 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2010.11.030