title: Mechanisms of isoproterenol-induced cardiac mitochondrial damage: protective actions of melatonin.
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.
authors: Oxidative stress and Free Radical Biology Laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, Kolkata, India; National Centre for Cell Science, Ganeshkhind, Pune, India.
authors: Debasri
authors: D
authors: Mukherjee
authors: Arnab K
authors: AK
authors: Ghosh
authors: Mousumi
authors: M
authors: Dutta
authors: Elina
authors: E
authors: Mitra
authors: Sanjaya
authors: S
authors: Mallick
authors: Bhaskar
authors: B
authors: Saha
authors: Russel J
authors: RJ
authors: Reiter
authors: Debasish
authors: D
authors: Bandyopadhyay
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D006041:Goats; D007545:Isoproterenol / Q000009:adverse effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D008550:Melatonin; D007545:Isoproterenol
keywords: antioxidant; in vitro; isoproterenol; melatonin; mitochondria