Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemiareperfusion: role of cardiolipin

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.

Metformin promotes isolated rat liver mitochondria impairment

“…Lipid peroxidation is a process whereby free radicals ''steal'' electrons from the lipids, resulting in cell damage and increased production of free radicals [33]. Recently, Majithiya and Balaraman [34] reported that metformin protects liver, kidney and aorta tissues against lipid peroxidation promoted by streptozotocin-induced diabetes.…”

Accelerated Mitochondrial Adenosine Diphosphate/Adenosine Triphosphate Transport Improves Hypertension-Induced Heart Disease

“…23 Mitochondrial ATP synthase activity was determined according to Yamada and Huzel 24 using the ATP Bioluminescence Assay Kit CLSII from Roche (Mannheim, Germany) as the ATP detection system. The respiratory control ratio was determined as described by Petrosillo et al 25 with a Clark-type oxygen electrode (H. Saur, Reutlingen, Germany) and succinate as the respiratory substrate.…”

Wine and heart health: learning from the French paradox

“…(32,33) Experimental data suggest that a high concentration of melatonin (40mg/L) confers anti-ischemic effects via its powerful antioxidant properties. (34,35) Our studies have shown that a low concentration of melatonin (corresponding to the concentration found in red wine), protects the heart against a lethal ischaemia-reperfusion injury in a rat model ( Figure 3). (36) Both melatonin and resveratrol confer cardioprotection via the activation of the recently discovered Survivor Activating Factor Enhancement (SAFE) pathway.…”