Melatonin protects against isoproterenol‐induced myocardial injury in the rat: antioxidative mechanisms

Abstract:  The present study was undertaken to explore the protective effect of melatonin against isoproterenol bitartrate (ISO)‐induced myocardial injury in rat. Treatment of rats with ISO increased the level of lipid peroxidation products and decreased the reduced glutathione levels in cardiac tissue indicating that this synthetic catecholamine induces oxidative damage following oxidative stress. Pretreatment of ISO‐injected rats with melatonin at a dose of 10 mg/kg body weight, i.p. prevented these changes. Additionally, melatonin also restored the activities and the levels of antioxidant enzymes which were found to be altered by ISO treatment. Treatment of rats with ISO resulted into an increased generation of hydroxyl radicals with melatonin pretreatment significantly reducing their production. Finally, treatment of rats with ISO caused a lowering of systolic pressure with reduced cardiac output and diastolic dysfunction whereas melatonin pretreatment significantly restored many of these parameters to normal. The findings document melatonin’s ability to provide cardio protection at a low pharmacological dose. Melatonin has virtually no toxicity which raises the possibility of this indole being a therapeutic treatment for ischemic heart disease.

[1]  R. Reiter,et al.  Kynuramines, metabolites of melatonin and other indoles: the resurrection of an almost forgotten class of biogenic amines , 2009, Journal of pineal research.

[2]  N. Banik,et al.  Therapeutic potential of melatonin in traumatic central nervous system injury , 2009, Journal of pineal research.

[3]  R. Reiter,et al.  Reducing oxidative/nitrosative stress: a newly-discovered genre for melatonin , 2009, Critical reviews in biochemistry and molecular biology.

[4]  D. Mukherjee,et al.  Excess of Glucocorticoid Induces Cardiac Dysfunction via Activating Angiotensin II Pathway , 2009, Cellular Physiology and Biochemistry.

[5]  R. Reiter,et al.  Clinical aspects of melatonin. , 2008, Saudi medical journal.

[6]  F. Peyrot,et al.  Potential role of tryptophan derivatives in stress responses characterized by the generation of reactive oxygen and nitrogen species , 2008, Journal of pineal research.

[7]  L. Rodella,et al.  Cardiovascular diseases: protective effects of melatonin , 2007, Journal of pineal research.

[8]  J. Kaski,et al.  A unicenter, randomized, double-blind, parallel-group, placebo-controlled study of Melatonin as an Adjunct in patients with acute myocaRdial Infarction undergoing primary Angioplasty The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial: study design and rat , 2007, Contemporary clinical trials.

[9]  R. Reiter,et al.  Melatonin reduces ventricular arrhythmias and preserves capillary perfusion during ischemia‐reperfusion events in cardiomyopathic hamsters , 2007, Journal of pineal research.

[10]  R. Reiter,et al.  One molecule, many derivatives: A never‐ending interaction of melatonin with reactive oxygen and nitrogen species? , 2007, Journal of pineal research.

[11]  D. Bandyopadhyay,et al.  Melatonin protects against oxidative damage and restores expression of GLUT4 gene in the hyperthyroid rat heart , 2007, Journal of pineal research.

[12]  D L Prior,et al.  Load-sensitive measures may overestimate global systolic function in the presence of left ventricular hypertrophy: a comparison with load-insensitive measures. , 2006, American journal of physiology. Heart and circulatory physiology.

[13]  D. Bandyopadhyay,et al.  Reactive oxygen species-induced gastric ulceration: protection by melatonin. , 2006, Current medicinal chemistry.

[14]  D. Malińska,et al.  Melatonin attenuates diabetes‐induced oxidative stress in rabbits , 2006, Journal of pineal research.

[15]  D. Bandyopadhyay,et al.  Vitamin E in the prevention of ischemic heart disease. , 2006, Pharmacological reports : PR.

[16]  R. Reiter,et al.  Melatonin mitigates mitochondrial malfunction , 2005, Journal of pineal research.

[17]  Debashis Bandyopadhyay,et al.  Melatonin protects against piroxicam‐induced gastric ulceration , 2004, Journal of pineal research.

[18]  D. Bandyopadhyay,et al.  Oxidative stress-induced ischemic heart disease: protection by antioxidants. , 2004, Current medicinal chemistry.

[19]  M. Buyukokuroglu,et al.  Protective effects of melatonin against myocardial injury induced by isoproterenol in rats , 2003, Journal of pineal research.

[20]  R. Reiter,et al.  Melatonin: a novel protective agent against oxidative injury of the ischemic/reperfused heart. , 2003, Cardiovascular research.

[21]  R. Reiter,et al.  Mechanistic and comparative studies of melatonin and classic antioxidants in terms of their interactions with the ABTS cation radical , 2003, Journal of pineal research.

[22]  D. Bandyopadhyay,et al.  Effect of isoproterenol on lipid peroxidation and antioxidant enzymes of myocardial tissue of mice and protection by quinidine , 2003, Molecular and Cellular Biochemistry.

[23]  R. Reiter,et al.  Melatonin: reducing the toxicity and increasing the efficacy of drugs , 2002, The Journal of pharmacy and pharmacology.

[24]  P. K. Das,et al.  Melatonin protects against gastric ulceration and increases the efficacy of ranitidine and omeprazole in reducing gastric damage , 2002, Journal of pineal research.

[25]  J. Sastre,et al.  Xanthine oxidase is involved in free radical production in type 1 diabetes: protection by allopurinol. , 2002, Diabetes.

[26]  R. Reiter,et al.  Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. , 2002, Current topics in medicinal chemistry.

[27]  L. Tesoriere,et al.  Oxidation of melatonin by oxoferryl hemoglobin: A mechanistic study , 2001, Free radical research.

[28]  R. Reiter Melatonin: Lowering the High Price of Free Radicals. , 2000, News in physiological sciences : an international journal of physiology produced jointly by the International Union of Physiological Sciences and the American Physiological Society.

[29]  D. Pompon,et al.  Nitrosation of melatonin by nitric oxide and peroxynitrite , 2000, Journal of pineal research.

[30]  K. Okumura,et al.  Melatonin scavenges hydroxyl radical and protects isolated rat hearts from ischemic reperfusion injury. , 2000, Life sciences.

[31]  V. Preedy,et al.  Oxidants, antioxidants and alcohol: implications for skeletal and cardiac muscle. , 1999, Frontiers in bioscience : a journal and virtual library.

[32]  Gordon H. Purser,et al.  Identification of the factors affecting the rate of deactivation of hypochlorous acid by melatonin. , 1999, Biochemical and Biophysical Research Communications - BBRC.

[33]  V. Vallyathan,et al.  Scavenging of reactive oxygen species by melatonin. , 1998, Biochimica et biophysica acta.

[34]  R. Reiter,et al.  Ischemia/reperfusion‐induced arrhythmias in the isolated rat heart: Prevention by melatonin , 1998, Journal of pineal research.

[35]  Y. Ho,et al.  Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice. , 1998, Journal of molecular and cellular cardiology.

[36]  S. Cuzzocrea,et al.  Protective effect of melatonin on cellular energy depletion mediated by peroxynitrite and poly (ADP‐ribose) synthetase activation in a non‐septic shock model induced by zymosan in the rat , 1998, Journal of pineal research.

[37]  H. Bittner,et al.  Physiologic effects of extracellular superoxide dismutase transgene overexpression on myocardial function after ischemia and reperfusion injury. , 1998, The Journal of thoracic and cardiovascular surgery.

[38]  A. Bindoli,et al.  Biochemical and toxicological properties of the oxidation products of catecholamines. , 1992, Free radical biology & medicine.

[39]  J. Martín,et al.  Negative and positive assays of superoxide dismutase based on hematoxylin autoxidation. , 1987, Archives of biochemistry and biophysics.

[40]  A. Swaak,et al.  Superoxide-dependent and -independent mechanisms of iron mobilization from ferritin by xanthine oxidase. Implications for oxygen-free-radical-induced tissue destruction during ischaemia and inflammation. , 1986, The Biochemical journal.

[41]  P. Vanhoutte,et al.  Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle. , 1986, The American journal of physiology.

[42]  N. Dhalla,et al.  Role of free radicals in catecholamine-induced cardiomyopathy. , 1982, Canadian journal of physiology and pharmacology.

[43]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[44]  I. Fridovich,et al.  Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). , 1969, The Journal of biological chemistry.

[45]  C F STRITTMATTER,et al.  STUDIES ON AVIAN XANTHINE DEHYDROGENASES. PROPERTIES AND PATTERNS OF APPEARANCE DURING DEVELOPMENT. , 1965, The Journal of biological chemistry.

[46]  P. Handler,et al.  XANTHINE OXIDASE. VI. INFLUENCE OF PH ON SUBSTRATE SPECIFICITY. , 1964, The Journal of biological chemistry.

[47]  I W SIZER,et al.  A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. , 1952, The Journal of biological chemistry.

[48]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[49]  R. Reiter,et al.  Melatonin and cardiac pathophysiology , 2009 .

[50]  Sukru Oter,et al.  Melatonin: An Established Antioxidant Worthy of Use in Clinical Trials , 2009, Molecular medicine.

[51]  R. Reiter,et al.  Relation of nocturnal melatonin levels to serum matrix metalloproteinase-9 concentrations in patients with myocardial infarction. , 2007, Thrombosis research.

[52]  R. Reiter,et al.  Biochemical reactivity of melatonin with reactive oxygen and nitrogen species , 2007, Cell Biochemistry and Biophysics.

[53]  R. Reiter,et al.  Melatonin Protects the Heart against both Ischemia/Reperfusion Injury and Chemotherapeutic Drugs , 2004, Cardiovascular Drugs and Therapy.

[54]  B. Lucchesi,et al.  Modulation of leukocyte-mediated myocardial reperfusion injury. , 1990, Annual review of physiology.

[55]  J. Segura-Aguilar,et al.  On the mechanism of the Mn3(+)-induced neurotoxicity of dopamine:prevention of quinone-derived oxygen toxicity by DT diaphorase and superoxide dismutase. , 1989, Chemico-biological interactions.

[56]  B. Halliwell,et al.  The importance of free radicals and catalytic metal ions in human diseases. , 1985, Molecular aspects of medicine.

[57]  S. Aust,et al.  Microsomal lipid peroxidation. , 1978, Methods in enzymology.

[58]  J. Sedlák,et al.  Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. , 1968, Analytical biochemistry.