Enhanced oxidative stress and impairments in nitric oxide synthesis and bioavailability
are of considerable importance in the pathogenesis of diabetic vascular diseases.
The aim of the present work was to evaluate the metabolic effects of pharmacological
doses of the melatonin, a known antioxidant, on streptozotocin-induced diabetic damage
in rats. We investigated the indolamine's influence on the cellular redox-balance,
nitric oxide (NO) level, and the activities of antioxidative defence enzymes, as well
as the activities of enzymes involved in phase II detoxication and NADPH-generating
pentose phosphate pathway. Blood glucose, glycated hemoglobin, bilirubin, as well
as plasma alanine aminotransferase activities increased and body weight was reduced
in rats with streptozotocin-induced (60 mg/kg, i.p.) diabetes (25 days). The NO level
was markedly increased in diabetic plasma (by 50%) and aortic tissue (by 30%). The
hyperglycemia resulted in reduced activities of glutathione peroxidase (by 25%), catalase
(by 20%), glucose-6-phosphate dehydrogenase (by 55%) and transketolase (by 40%) 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. The most pronounced effect of the melatonin administration was the
prevention of 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.