Melatonin protects against isoproterenol-induced alterations in cardiac mitochondrial energy-metabolizing enzymes, apoptotic proteins, and assists in complete recovery from myocardial injury in rats.
The present study was undertaken to explore the protective effect of melatonin against isoproterenol bitartrate (ISO)-induced rat myocardial injury and to test whether melatonin has a role in preventing myocardial injury and recovery when the ISO-induced stress is withdrawn. Treatment for rats with ISO altered the activities of some of the key mitochondrial enzymes related to energy metabolism, the levels of some stress proteins, and the proteins related to apoptosis. These changes were found to be ameliorated when the animals were pretreated with melatonin at a dose of 10 mg/kg BW, i.p. In addition to its ability to reduce ISO-induced mitochondrial dysfunction, we also studied the role of melatonin in the recovery of the cardiac tissue after ISO-induced damage. Continuation of melatonin treatment in rats after the withdrawal of ISO treatment was found to reduce the activities of cardiac injury biomarkers including serum glutamate oxaloacetate transaminase (SGOT), lactate dehydrogenase (LDH), and cardio-specific LDH1 to control levels. The levels of tissue lipid peroxidation and reduced glutathione were also brought back to that seen in control animals by continued melatonin treatment. Continuation of melatonin treatment in post-ISO treatment period was also found to improve cardiac tissue morphology and heart function. Thus, the findings indicate melatonin’s ability to provide cardio protection at a low pharmacological dose and its role in the recovery process. Melatonin, a molecule with very low or no toxicity may be considered as a therapeutic for the treatment for ischemic heart disease.
Oxidative Stress and Free Radical Biology Laboratory, Department of Physiology, University College of Science and Technology, University of Calcutta, Kolkata, India.
Debasri
D
Mukherjee
Arnab K
AK
Ghosh
Arun
A
Bandyopadhyay
Anjali
A
Basu
Santanu
S
Datta
Sanjib K
SK
Pattari
Russel J
RJ
Reiter
Debasish
D
Bandyopadhyay
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007545:Isoproterenol / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000097:blood / Q000378:metabolism; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D017202:Myocardial Ischemia / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D007527:Isoenzymes; D008054:Lipid Peroxides; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1; D001219:Aspartate Aminotransferases; D005978:Glutathione; D008550:Melatonin; D007545:Isoproterenol