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Updated: Jan 30, 2026
In Vitro Assessment of Cardiac Function Using Skinned Cardiomyocytes
Published on: June 22, 2020
The effect of melatonin on digoxin‑induced cardiac damage in cardiomyocytes
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).
Insights
Melatonin reduces digoxin toxicity by modulating Transient receptor potential vanilloid 1 (TRPV1) channels in cardiomyocytes. This study shows melatonin
Area of Science:
- Cardiovascular Medicine
- Cell Biology
- Pharmacology
Background:
- Digoxin, a cardiac glycoside, is widely used but can cause toxicity.
- Digoxin toxicity involves oxidative stress and intracellular calcium overload.
- Transient receptor potential vanilloid 1 (TRPV1) channels in cardiomyocytes are activated by reactive oxygen species.
Purpose of the Study:
- Investigate digoxin toxicity effects on cardiomyocytes.
- Examine alterations in calcium influx, oxidative stress, and apoptosis via TRPV1 channels.
- Evaluate the cardioprotective role of melatonin in digoxin toxicity.
Main Methods:
- Cardiomyocytes were divided into seven groups, including control, digoxin, and melatonin-treated groups.
- TRPV1 channels were activated or inhibited using capsaicin and capsazepine.
- Measurements included cytosolic calcium, reactive oxygen species, mitochondrial depolarization, and caspase levels.
Main Results:
- Melatonin significantly reduced apoptosis in digoxin-treated cardiomyocytes.
- Cell viability was enhanced in groups treated with digoxin and melatonin, or digoxin and capsazepine.
- Melatonin and TRPV1 inhibition improved cell viability and reduced apoptosis during digoxin toxicity.
Conclusions:
- TRPV1 channels are overactivated during digoxin toxicity.
- Melatonin demonstrates a cardioprotective effect by modulating TRPV1 channels.
- Targeting TRPV1 channels with melatonin may be a therapeutic strategy for digoxin toxicity.
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