Melatonin affords protection against myocardial ischemia-induced cerebral mitochondrial dysfunction: an in vivo study

Background: Ischemic Heart Disease (IHD) is a health problem of global concern. The studies on myocardial ischemia induced changes in brain particularly cerebrum portion are scanty. Lacunae exist in the knowledge whether such changes can be protected by antioxidant(s). The present work was carried out to explore the ameliorating potential of melatonin against isoproterenol induced changes in tissue and mitochondria isolated from heart and brain of male Wistar rats. Methods: The adverse changes were induced by administering isoproterenol bitartrate subcutaneously at a dose of 25mg/kg body weight. Protective effects of melatonin was examined by administering melatonin at the dose of 40mg / kg body weight. After the treatment period, biomarkers of organ damage and oxidative stress biomarkers, activities of mitochondrial antioxidant as well as Kreb’s cycle enzymes, and tissue and mitochondrial morphology was studied. Results: Isoproterenol administration caused remarkable deleterious changes in oxidative stress biomarkers like lipid peroxidation level, reduced glutathione and protein carbonyl content of tissue and mitochondria. Moreover, isoproterenol unfavorably altered the activity of antioxidant enzymes like Mn-SOD, glutathione peroxidase (GPx) and glutathione reductase (GR) in mitochondria thus confirming the generation of oxidative stress in mitochondria. Altered activity of some of the important Kreb’s cycle enzymes indicated the disturbance in energy metabolism. The degeneration of mitochondria was observed by scanning electron microscopy and fluorescence confocal microscopy. Melatonin pre-treatment successfully restored all the parameters to normal level at a dose of 40mg/kg body weight. Conclusion: Isoproterenol causes deleterious changes in cardiac and cerebrum portion of the brain tissue as well as the mitochondria and melatonin pre-treatment protects against such changes. Thus, therapeutic use of melatonin may be considered in treating cardiovascular diseases along with subsequent brain damages as there may be strong relationship between cardiovascular diseases and cognitive functioning of brain.