RESEARCH ARTICLE Melatonin improves hyperglycemia induced damages in rat brain Begum Gurel‐Gokmen 1 | Hazal Ipekci 1 | Sehkar Oktay 1 | Burcın Alev 1 | Unsal Velı Ustundag 1 | Esın Ak 2 | Dılek Akakın 3 | Goksel Sener 4 | Ebru Emekli‐Alturfan 1 | Aysen Yarat 1 | Tugba Tunali‐Akbay 1 1 Basic Medical Sciences, Biochemistry, Marmara University, Faculty of Dentistry, Istanbul, Turkey 2 Basic Medical Sciences, Histology and Embryology, Marmara University, Faculty of Dentistry, Istanbul, Turkey 3 Basic Medical Sciences, Histology and Embryology, Marmara University, Faculty of Medicine, Istanbul, Turkey 4 Pharmacology, Marmara University, Faculty of Pharmacy, Istanbul, Turkey Correspondence Tugba Tunali‐Akbay, Marmara University, Faculty of Dentistry, Basic Medical Sciences, Biochemistry, Istanbul, Turkey. Email: ttunali@marmara.edu.tr Abstract Background: Diabetes mellitus is an endocrine disorder which is characterized by the development of resistance to the cellular activity of insulin or inadequate insulin production. It leads to hyperglycemia, prolonged inflammation, and oxidative stress. Oxidative stress is assumed to play an important role in the development of diabetic complications. Melatonin is the hormone that interacts with insulin in diabetes. Therefore, in this study, the effects of melatonin treatment with or without insulin were examined in diabetic rat brain. Methods: Rats were divided into five groups as control, diabetes, diabetes + insulin, diabetes + melatonin, and diabetes + melatonin + insulin. Experimental diabetes was induced by streptozotocin (60 mg/kg, i.p.). Twelve weeks after diabetes induction, rats were decapitated. Malondialdehyde, glutathione, sialic acid and nitric oxide levels, superoxide dismutase, catalase, glutathione‐S‐transferase, myeloperoxidase, and tissue factor activities were determined in brain tissue. Results: Melatonin alone showed its antioxidant effect by increasing brain glutathi- one level, superoxide dismutase, catalase, and glutathione‐S‐transferase activities and decreasing malondialdehyde level in experimental diabetes. Although insulin did not have a significant effect on glutathione and glutathione‐S‐transferase, its effects on lipid peroxidation, superoxide dismutase, and catalase were similar to melatonin; insulin also decreased myolopeoxidase activity and increased tissue factor activity. Combined melatonin and insulin treatment mimicked the effects of insulin. Conclusion: Addition of melatonin to the insulin treatment did not change the effects of insulin, but the detailed role of melatonin alone in the treatment of diabetes merits further experimental and clinical investigation. KEYWORDS brain, diabetes, insulin, melatonin, oxidative stress 1 | INTRODUCTION Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from deficient insulin secretion, insulin action, or both. 1 Chiefly, carbohydrate, lipid, and protein metabolism deteriorates, and various long‐term complications appear in diabetes. 2 Persistent hyperglycemia can generate oxygen species and cause neuroinflammation in the brain. 3,4 Hippocampal injury, reduction in gray matter density, changes in white matter microstructure, and atrophy in brain structure have been reported in patients with Received: 12 March 2018 Revised: 14 June 2018 Accepted: 30 July 2018 DOI: 10.1002/dmrr.3060 Diabetes Metab Res Rev. 2018;34:e3060. https://doi.org/10.1002/dmrr.3060 © 2018 John Wiley & Sons, Ltd. wileyonlinelibrary.com/journal/dmrr 1 of 10