Yonsei Med J.  2008 Oct;49(5):735-741. 10.3349/ymj.2008.49.5.735.

The Effect of High Dose Melatonin on Cardiac Ischemia-reperfusion Injury

• Ceyran H
• Narin F
• Narin N
• Akgun H
• Ceyran AB
• Ozturk F
• Akcali Y

• KMID: 2158191
• DOI: http://doi.org/10.3349/ymj.2008.49.5.735

Abstract

PURPOSE
Melatonin, the most potent scavenger of toxic free radicals, has been found to be effective in protecting against pathological states due to the release of reactive oxygen species. This study was performed to establish the effect of high dose melatonin on protection against ischemia- reperfusion (I/R) injury in rat hearts. MATERIALS AND METHODS: Forty male Sprague-Dawley rats were used in this study. They were separated into four groups of ten rats each. A left coronary artery occlusion was induced in the rats by ligating the artery for 20 minutes and then releasing the ligation (reperfusion) afterwards. The control group was Group A. Group B was subjected to myocardial ischemia-reperfusion without any treatment, while Group C underwent myocardial ischemia-reperfusion with a melatonin treatment before the ischemia. Group D was subjected to myocardial ischemia-reperfusion with a melatonin treatment before the reperfusion. After 20 minutes of reperfusion, blood samples were obtained from each group for biochemical studies, and the animals were sacrificed for histological and, immunohistochemical examinations of the myocardial tissue. RESULTS: We found that the cardiac troponin T(cTn-T) levels were significantly increased in Group B when all groups were compared. In the Group C rats treated with melatonin, the cTn-T values were significantly lower than those in Groups B and D. In addition, malondialdehyde (MDA) and antioxidant enzymes including, superoxide dismutase (SOD) and myeloperoxidase (MPO) were lower than those in Group B in the melatonin treated groups. The differences were statistically significant (p < 0.05). Histopathologic and immunohistopathologic studies also supported the effectiveness of melatonin. CONCLUSION: Our study suggests that high dose melatonin, appears to offer protection against cardiac ischemia-reperfusion injuries in rats by scavenging the free radicals and could have a potential clinical use in the management of myocardial ischemia.

Keyword

Melatonin; myocardial ischemia-reperfusion; antioxidant; Fas and Bcl-2 expression

MeSH Terms

Animals
Antioxidants/administration & dosage/*therapeutic use
Male
Malondialdehyde/metabolism
Melatonin/administration & dosage/*therapeutic use
Myocardial Reperfusion Injury/*drug therapy/pathology
Peroxidase/metabolism
Rats
Rats, Sprague-Dawley
Superoxide Dismutase/metabolism
Troponin/metabolism

Figure

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  Fig. 1 Melatonin treatment was associated with decrease Fas expression while Bcl-2 expression were significantly higher in ischemic-reperfused hearts in rats Groups C and D.

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  Fig. 2 Strong immunoreactivity with Bcl-2 in myofibrilles in Group C (IHK × 200).

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  Fig. 3 Severe edema among myofibrilles in non-treated melatonin Group B (H & E × 200).

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  Fig. 4 Minimal edema among myofibrilles in treated melatonin Group C (H & E × 100).

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