Melatonin ameliorates diabetes-induced brain injury in rats

Abstract

Diabetic brain is a serious complication of diabetes, and it is associated with oxidative stress and neuronal injury. This study investigated the protective effect of melatonin (MLT) on diabetes-induced brain injury. A rat model of type 2 diabetes mellitus was produced by intraperitoneal injection of nicotinamide 100 mg/kg, followed by intraperitoneal injection of streptozotocin 55 mg/kg. The diabetic rats were orally administered MLT 10 mg/kg of body weight for 15 days. MLT remarkably downregulated serum glucose levels. It also improved levels of the lipid peroxidation product 4-hydroxynonenal, improved levels of antioxidants including glutathione, glutathione peroxidase and glutathione reductase in the brains of the diabetic rats, and this is indicative of the antioxidant potential of MLT. MLT also prevented increase in homocysteine, amyloid-β42 and tau levels in diabetic rats, and this suggests that it can reduce the risk of dementia. This is associated with reduction in the levels of the dopamine, serotonin, and glutamate and is indicative of the regulatory effect of MLT on neurotransmitters. Treatment with MLT improved diabetes-induced structural alteration in the hippocampus and cerebral cortex. MLT significantly reduced caspase-3 and Bax as well as significantly increase Bcl-2 protein and GFAP-positive astrocytes indicating its anti-apoptotic effect. MLT showed remarkable ameliorative effect against biochemical and molecular alterations in the brains of diabetic rats most likely through its antioxidant property.