Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats

Elena Ju Sudnikovich, Yuri Z. Maksimchik, Svetlana V. Zabrodskaya, Valeri L. Kubyshin, Elena A. Lapshina, Maria Bryszewska, Russel J. Reiter, Ilya B. Zavodnik

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)180-187
Number of pages8
JournalEuropean Journal of Pharmacology
Volume569
Issue number3
DOIs
StatePublished - Aug 27 2007

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Keywords

  • Diabetes
  • Melatonin
  • Nitric oxide
  • Nitrosomelatonin

ASJC Scopus subject areas

  • Pharmacology

Cite this

Sudnikovich, E. J., Maksimchik, Y. Z., Zabrodskaya, S. V., Kubyshin, V. L., Lapshina, E. A., Bryszewska, M., Reiter, R. J., & Zavodnik, I. B. (2007). Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats. European Journal of Pharmacology, 569(3), 180-187. https://doi.org/10.1016/j.ejphar.2007.05.018