Melatonin and succinate reduce rat liver mitochondrial dysfunction in diabetes

Ilya B. Zavodnik, E. A. Lapshina, V. T. Cheshchevik, I. K. Dremza, J. Kujawa, S. V. Zabrodskaya, R. J. Reiter

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Mitochondrial dysfunction and an increase in mitochondrial reactive oxygen species in response to hyperglycemia during diabetes lead to pathological consequences of hyperglycemia. The aim of the present work was to investigate the role of a specific functional damage in rat liver mitochondria during diabetes as well as to evaluate the possibility of metabolic and antioxidative correction of mitochondrial disorders by pharmacological doses of succinate and melatonin. In rat liver mitochondria, streptozotocin-induced diabetes was accompanied by marked impairments of metabolism: we observed a significant activation of α-ketoglutarate dehydrogenase (by 60%, p<0.05) and a damage of the respiratory function. In diabetic animals, melatonin (10 mg/kg b.w., 30 days) or succinate (50 mg/kg b.w., 30 days) reversed the oxygen consumption rate V 3 and the acceptor control ratio to those in nondiabetic animals. Melatonin enhanced the inhibited activity of catalase in the cytoplasm of liver cells and prevented mitochondrial glutathione-S-transferase inhibition while succinate administration prevented α-ketoglutarate dehydrogenase activation. The mitochondria dysfunction associated with diabetes was partially remedied by succinate or melatonin administration. Thus, these molecules may have benefits for the treatment of diabetes. The protective mechanism may be related to improvements in mitochondrial physiology and the antioxidative status of cells.

Original languageEnglish (US)
Pages (from-to)421-427
Number of pages7
JournalJournal of Physiology and Pharmacology
Volume62
Issue number4
StatePublished - Aug 1 2011

Keywords

  • Antioxidants
  • Bioenergetics
  • Experimental diabetes
  • Liver
  • Melatonin
  • Mitochondria
  • Succinate

ASJC Scopus subject areas

  • Physiology
  • Pharmacology

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