In most species studied, melatonin is an indolamine hormone, mainly secreted by the pineal gland into the blood circulation. Melatonin has properties of both direct and indirect powerful antioxidants. The aim of the present work was to evaluate radical-scavenging properties and the metabolic effects of pharmacological doses of the melatonin on streptozotocin-induced (60 mg/kg, i.p.) diabetic (25 days) damage in rats.

Melatonin at concentrations 100-2000 μM considerably inhibited the membrane lipid peroxidation in human erythrocytes treated with organic hydroperoxide in vitro as well as radical-induced generation of luminol-dependent chemiluminescence. The Stern-Volmer constant for inhibition of azo-initiator-derived peroxyl radical generation by melatonin was determined to be (0.42±0.05)x10⁴ M^-1.

Enhanced oxidative stress and impairments in nitric oxide synthesis and bioavailability are of considerable importance in the pathogenesis of diabetic vascular diseases. We investigated the indolamine’s influence on the cellular redox-balance, nitric oxide (NO) level, and the activities of antioxidative defence enzymes, i.e., those involved in phase II detoxication and NADPH-generating pentose phosphate pathway. Blood glucose, glycated haemoglobin, bilirubin, as well as plasma alanine aminotransferase activities increased and body weight was reduced in rats with diabetes. The NO level was markedly increased in diabetic plasma (by 50%) and aortic tissue (by 30%). The hyperglycaemia resulted in reduced activities of glutathione peroxidase, catalase, glucose-6-phosphate dehydrogenase and transketolase in liver tissue of diabetic animals.

Melatonin treatment (10 mg/kg, 18 days) did not influence the level of hyperglycemia or glycated hemoglobin and it had little effect on the activities of antioxidative enzymes. However, melatonin markedly reversed the activities of glucose-6-phosphate dehydrogenase and transketolase in liver tissue of diabetic rats and prevented an increase in nitric oxide levels in blood plasma and aortic tissue during diabetes. In in vitro experiments, nitrosomelatonin formation in the presence of nitrosodonors was observed. This implies that melatonin might operate as an NO scavenger and carrier. Thus, melatonin treatment may have some beneficial effects in controlling diabetic vascular complications.

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1. Effects of oxidative stress on rat liver and heart antioxidative defence and the pentose phosphate pathway enzymes in vitro and in vivo