Mechanisms of isoproterenol-induced cardiac mitochondrial damage: Protective actions of melatonin

Debasri Mukherjee, Arnab K. Ghosh, Mousumi Dutta, Elina Mitra, Sanjaya Mallick, Bhaskar Saha, Russel J. Reiter, Debasish Bandyopadhyay

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Mitochondrial dysfunction due to oxidative damage is the key feature of several diseases. We have earlier reported mitochondrial damage resulting from the generation of oxidative stress as a major pathophysiological effect of isoproterenol (ISO)-induced myocardial ischemia in rats. That melatonin is an antioxidant that ameliorates oxidative stress in experimental animals as well as in humans is well established. We previously demonstrated that melatonin provides cardioprotection against ISO-induced myocardial injury as a result of its antioxidant properties. The mechanism of ISO-induced cardiac mitochondrial damage and protection by melatonin, however, remains to be elucidated in vitro. In this study, we provide evidence that ISO causes dysfunction of isolated goat heart mitochondria. Incubation of cardiac mitochondria with increasing concentrations of ISO decreased mitochondrial succinate dehydrogenase (SDH) activity, which plays a pivotal role in mitochondrial bioenergetics, as well as altered the activities of other key enzymes of the Kreb's cycle and the respiratory chain. Co-incubation of ISO-challenged mitochondria with melatonin prevented the alterations in enzyme activity. That these changes in mitochondrial energy metabolism were due to the perpetration of oxidative stress by ISO was evident from the increased levels of lipid peroxidation and decreased reduced glutathione/oxidized glutathione ratio. ISO-induced oxidative stress also altered mitochondrial redox potential and brought about changes in the activity of the antioxidant enzymes manganese superoxide dismutase and glutathione peroxidase, eventually leading to alterations in total ATPase activity and membrane potential. Melatonin ameliorated these changes likely through its antioxidant abilities suggesting a possible mechanism of cardioprotection by this indole against ISO-induced myocardial injury.

Original languageEnglish (US)
Pages (from-to)275-290
Number of pages16
JournalJournal of pineal research
Volume58
Issue number3
DOIs
StatePublished - Apr 2015

Keywords

  • antioxidant
  • in vitro
  • isoproterenol
  • melatonin
  • mitochondria

ASJC Scopus subject areas

  • Endocrinology

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