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Melatonin protects against ischaemic-reperfusion myocardial damage
1MRC Experimental Biology Programme, University of Stellenbosch, Republic of South Africa.
Objectives:
Melatonin, a hormonal product of the pineal gland, is now known to be a multi-faceted free radical scavenger and anti-oxidant. Since little information is available regarding the action of melatonin on the heart, we studied the effects of melatonin on adult ventricular myocytes subjected to chemical hypoxia and reoxygenation.
Methods:
Adult rat ventricular myocytes were preloaded with tetramethylrhodamine (TMRM) in combination with one of the following fluorophores: dichlorodihydrofluorescein diacetate (DCDHF), dihydrorhodamine 123 (DHR) or fluo 3 (Fluo) and then investigated with confocal laser scanning microscopy. Chemical hypoxia was induced by addition of 1.5 mM KCN and 20 mM deoxyglucose to the superfusion buffer. Melatonin (50-100 microM) was added at intervals during the protocol.
Results:
Cells subjected to 12.5 min chemical hypoxia showed marked morphological changes, increased fluorescence intensity of DCDHF, DHR and Fluo, suggesting Ca2+ accumulation and generation of H2O2 and reactive oxygen species. The number of cells showing increased fluorescence also increased significantly. Melatonin (50 and 100 microM) caused a significant reduction in morphological changes, number of cells with increased fluorescence and fluorescence intensity of DHR and Fluo, (but not DCDHF).
Conclusion:
Melatonin effectively reduced damage induced by chemical hypoxia in adult cardiomyocytes, probably by virtue of its effects on reactive oxygen species generation and intracellular Ca2+ accumulation.