Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia- reperfusion: role of cardiolipin
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Published on: April 16, 2018
G Petrosillo1, N Di Venosa, M Pistolese
1Department of Biochemistry and Molecular Biology and CNR Institute of Biomembranes and Bioenergetics, University of Bari, Bari Italy.
Abstract:
Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration, mainly at the level of complex I and III, is an important source of ROS generation and hence a potential contributor of cardiac reperfusion injury. Appropriate antioxidant strategies could be particularly useful to limit this ROS generation and associated mitochondrial dysfunction. Melatonin has been shown to effectively protect against ischemic-reperfusion myocardial damage. The mechanism by which melatonin exerts this cardioprotective effect is not well established. In the present study we examined the effects of melatonin on various parameters of mitochondrial bioenergetics in a Langerdoff isolated perfused rat heart model. After isolation of mitochondria from control, ischemic-reperfused and melatonin-treated ischemic-reperfused rat heart, various bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, complex I and complex III activity, H2O2 production as well as the degree of lipid peroxidation, cardiolipin content, and cardiolipin oxidation. We found that reperfusion significantly altered all these mitochondrial parameters, while melatonin treatment had strong protective effect attenuating these alterations. This effect appears to be due, at least in part, to the preservation, by ROS attack, of the content and integrity of cardiolipin molecules which play a pivotal role in mitochondrial bioenergetics. Protection of mitochondrial dysfunction was associated with an improvement of post-ischemic hemodynamic function of the heart. Melatonin had also strong protective effect against oxidative alterations to complex I and III as well as to cardiolipin in isolated mitochondria.
Insights
Melatonin protects the heart from ischemia/reperfusion injury by preserving mitochondrial function and cardiolipin integrity. This antioxidant strategy limits reactive oxygen species (ROS) generation, improving cardiac bioenergetics and hemodynamic function.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Medicine
- Oxidative Stress Research
Background:
- Ischemia/reperfusion (I/R) injury in cardiac myocytes involves reactive oxygen species (ROS).
- Mitochondrial respiration, particularly complexes I and III, is a key source of ROS, contributing to cardiac reperfusion injury.
- Antioxidant strategies are crucial for limiting ROS generation and mitochondrial dysfunction.
Purpose of the Study:
- To investigate the protective mechanisms of melatonin against I/R-induced mitochondrial dysfunction in the heart.
- To evaluate the effects of melatonin on mitochondrial bioenergetics, ROS production, and cardiolipin integrity.
Main Methods:
- Utilized a Langendorff isolated perfused rat heart model.
- Isolated mitochondria from control, I/R, and melatonin-treated I/R hearts.
- Assessed mitochondrial oxygen consumption, complex I and III activity, H2O2 production, lipid peroxidation, cardiolipin content, and oxidation.
Main Results:
- Reperfusion significantly altered mitochondrial parameters, including oxygen consumption, enzyme activities, and cardiolipin integrity.
- Melatonin treatment attenuated these I/R-induced alterations, preserving cardiolipin content and integrity against ROS attack.
- Melatonin protected mitochondrial complexes I and III and cardiolipin from oxidative damage.
- Improved mitochondrial function correlated with enhanced post-ischemic hemodynamic function.
Conclusions:
- Melatonin exerts a cardioprotective effect against I/R injury, partly by preserving mitochondrial bioenergetics and cardiolipin integrity.
- Melatonin's antioxidant properties mitigate ROS-induced damage to mitochondria, crucial for maintaining cardiac function.
- This study highlights melatonin as a potential therapeutic agent for limiting I/R injury through mitochondrial protection.
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