The effect of melatonin on digoxin-induced cardiac damage in cardiomyocytes

Abstract

OBJECTIVES: Digoxin is a cardiac glycoside which is widely used in cardiovascular medicine. Oxidative stress, as well as intracellular Ca2+ overload, plays an important role in digoxin toxicity. Transient receptor potential vanilloid 1 (TRPV1) channels are found in cardiomyocyte cells and they are activated by reactive oxygen species. We investigated the effects of digoxin toxicity and alterations in Ca2+ influx, oxidative stress and apoptosis through TRPV1 channels and modulator role of melatonin in cardiomyocytes. METHODS: The cells were divided into seven main groups as control, digoxin, digoxin+capsazepine, digoxin+melatonin, digoxin+capsazepine+melatonin, melatonin and melatonin+capsazepine groups. Cells in the groups were stimulated with capsaicin and inhibited with capsazepine in related experiments for activation and inactivation of TRPV1 channels, respectively. We measured cytosolic calcium, intracellular reactive oxygen, mitochondrial depolarization, caspase 9 and caspase 3 levels. RESULTS: The apoptosis values were significantly lower in the melatonin and digoxin+ melatonin groups than in the digoxin group of cardiomyocytes (p < 0.001). The cell viability values were higher in the digoxin+ capsazepine (p < 0.001), digoxin+melatonin (p < 0.001) and digoxin+melatonin+capsazepine (p < 0.001) groups than in the digoxin group. CONCLUSION: TRPV1 channels are overactivated during digoxin toxicity and melatonin could show a cardioprotective effect through TRPV1 channel modulation (Fig. 5, Ref. 56).