The investigation of the effects of melatonin and l-carnitine on oxidative stress and vascular responses in type 2 diabetic rat model

Tip 2 diabetes mellitus is a very common health disorder. Vascular dysfunction may play a major role in the pathogenesis of diabetic cardiovascular diseases. Mechanisms underlying the vascular dysfunction are multifactorial; hyperglycaemia, oxidative stress and dyslipidaemia are thought to be the important factors. Reduction in the antioxidant parameters and increased free radical formation contribute to the development of oxidative stress in diabetes and responsible in the development of diabetic complications. L-carnitine as well as melatonin were shown to possess strong antioxidant properties. Melatonin is a lipophilic indolamine derived from tryptophan, mainly produced from pineal gland and is considered to be the one of the most potent antioxidative agent. It has been shown that melatonin reduces streptozotocin (STZ) -induced oxidative stress in diabetic rats. L-Carnitine is a small water-soluble quaternary amine that plays an important role in lipid metabolism. In the diabetes a significant reduction in plasma carnitine levels has been shown, which suggests that L-carnitine may play an important role in the pathophysiology of diabetic complications. Diabetes induced with high fat diet (for 8 weeks) and multipl low doses intraperitoneal injection of STZ (twice, 30 mg/kg/ i.p). The diabetic animals were randomly assigned to one of the experimental groups as follows: Control group high fat diet (HFD) and STZ-induced diabetic group (HFD + STZ) , HFD + STZ diabetic group received L-carnitine (0.6 g/kg i.p), HFD + STZ diabetic group received melatonin (10mg/kg/g i.p) and HFD + STZ diabetic group received glibenclamide (5mg/kg/g oral). The serum fasting blood glucose, insulin, total cholesterol, HDL- cholesterol, LDL- cholesterol, triglyceride and malondialdehyde (MDA) level were tested. Acetylcholine-induced endothelium-dependent relaxation and sodium nitroprusside induced endothelium-independent relaxation were measured in aortas for estimating endothelial function. Also, glutathione peroxidase (GSH- Px), superoxide dismutase (SOD) and nitric oxide (NO) levels activities were determined in rat liver. According to our results. melatonin and L carnitin treatment significantly increased fasting blood glucose, total colesterol, and LDL levels. MDA levels significantly decreased with the melatonin treatment whereas SOD levels were not significantly changed between the groups. The results showed that especially melatonin restores the vascular responses and endothelial dysfunction in diabetes.