Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats.
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.
Sudnikovich
Elena Ju
EJ
State Research and Innovation Center, Institute for Pharmacology and Biochemistry of the National Academy of Sciences of Belarus, BLK-50, 230017 Grodno, Belarus.
Maksimchik
Yuri Z
YZ
Zabrodskaya
Svetlana V
SV
Kubyshin
Valeri L
VL
Lapshina
Elena A
EA
Bryszewska
Maria
M
Reiter
Russel J
RJ
Zavodnik
Ilya B
IB
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000209:etiology; D009249:NADP / Q000096:biosynthesis; D009569:Nitric Oxide / Q000378:metabolism*; D009603:Nitroso Compounds / Q000378:metabolism; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014174:Transketolase / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D001786:Blood Glucose; D005954:Glucosephosphate Dehydrogenase; D006442:Glycated Hemoglobin; D008550:Melatonin; D009249:NADP; D009569:Nitric Oxide; D009603:Nitroso Compounds; D013311:Streptozocin; D014174:Transketolase; C503522:N1-nitrosomelatonin