The effects of melatonin on NRF-2 expression and oxidativestress in heart muscle and skeletal muscle in rats with experimentaldiabetes

Diabetes mellitus (DM) is an epidemic disease associated with chronic hyperglycemia. Chronic hyperglycemia is associated with the production of free oxygen radicals (ROS). Nuclear factor erythroid-2-related factor 2 (NRF2) is a redox sensitive transcription factor and controls gene production of many antioxidant enzymes. Melatonin has been shown to be protective in diabetic neuropathy in experimental models. The aim of this study was to investigate the effect of melatonin on NRF2 levels and oxidative stres levels in skeletal muscle and heart muscle in experimental diabetes-induced rats. 36 Wistar albino rats were divided into four groups. 1) Control+isotonic solution (SF) group (n=8), 2) control+melatonin group (n=8), 3) Diabetes+SF group (n=10), 4) Diabetes+melatonin group (n=10). A single dose of intraperitoneal streptozotocin (STZ) was administered at a dose of 60 mg/kg. Melatonin treatment (10 mg/kg, İP) was administered for 28 days. At the end of this period, malondialdehyde (MDA) level as an indicator of lipid peroxidation and reduced glutathione levels (GSH) were determined by spectrophotometry. NRF2 and thioredoxin (TRX) levels were measured by ELISA. MDA levels of the diabetic group were higher than the control groups and this value was significantly decreased after melatonin treatment (p<0.05). Skeletal muscle GSH levels in the melatonin treated diabetic group was significantly higher than the diabetic group. In the diabetic group, skeletal muscle NRF2 levels were found lower than normoglycemic control groups. Melatonin treatment increased this value to control levels. Although NRF2 levels of heart muscle in the diabetes group was found to be decreased, the differences was not statistically significant. No difference was observed between the groups in skeletal muscle in TRX levels. In the diabetes group, heart muscle TRX levels were lower than control groups and melatonin administration increased this level (p<0.05). The results of our study indicate that melatonin treatment can reduce the oxidative stres induced with diabetes by NRF2 pathway in skeletal muscle and by TRX pathway in cardiac muscle.