INFLUENCE OF MELATONIN ON AGE-RELATED CHANGES IN CARBOHYDRATE METABOLISM AND ANTIOXIDANT CAPACITY IN THE BLOOD OF ALLOXAN DIABETIC RATS

Abstract

Melatonin and its metabolites have potent antioxidant/anti-inflammatory properties, and they have proven to be highly effective in a variety of disorders linked to inflammation and oxidative stress. The object of this experimental research was to ascertain the influence of aging on the level of basal glycemia and activities of glucose-6-phosphate dehydrogenase [EC1.1.1.49], pyruvate kinase [EC 2.7.1.40] and glutathione reductase [EC1.6.4.2] in erythrocytes of alloxan diabetic rats on the background of melatonin injections. Methods: We used 100 male Wistar rats, two age groups: the - 2-month (adult), and II - 4-month (old). Alloxan diabetes was evoked via injecting the rats with a 5% solution of alloxan monohydrate intraperitoneally in a dose of 170 mg/kg. Four days after diabetes induction, rats were divided into diabetic (untreated) and melatonin-diabetic group (10 mg/kg, daily and intraperitoneally for six weeks). Blood was taken from the tail vein evaluate the basal glycemia on 5-th and 47-th day after the injection of alloxan. Rats were sacrificed at the 47-th day of the experiment accordance with the ethical treatment of animals. Determinations of the enzymes activities were by standard methods. Statistical analysis was performed using Statistica 10 StatSoft Inc. Results. The level of basal glycemia on the fifth day of the experiment in animals of both groups increased on average by 115% from baseline values. We founded that on 47-th day this index was higher in group of old rats on 20% more than in adult rats. Pyruvate kinase activity in erythrocytes of adult and old animals with diabetes decreased by 34% and 51% respectively compared with the control. glucose-6-phosphate dehydrogenase activity in erythrocytes of adult and old animals with diabetes decreased by 25% and 44% respectively compared with the control on 47-th day. The changes may be the result of age-related disorders of glucose metabolism due to disturbances in free radical mechanisms. Glutathione reductase activity in erythrocytes of adult and old animals with diabetes decreased by 30% and 36% respectively compared with the control on 47-th day. A 42-days injection of melatonin to the alloxan diabetic rats of both groups contributed to a normalization of the level of basal glycemia, the activities of pyruvate kinase and glutathione reductase in the rat blood, as well as to a considerable increase of the activity of glucose-6-phosphate dehydrogenase, whose level exceeded by average 9% this particular index in the control group of animals. Under the influence of melatonin increase activity of glucose-6-phosphate dehydrogenase in the blood of rats may be due to the increasing number of substrate for glucose-6-phosphate dehydrogenase (stimulating the flow of glucose into cells and its phosphorylation) and direct action. Conclusion. In this case melatonin probably increases use of glucose for regeneration of NADPH2 and aerobic oxidation of glucose that indicate an acceleration of antioxidative protection and energy production in blood of adult and old diabetic rats.