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Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemiareperfusion: role of cardiolipin
Author(s) -
Petrosillo G.,
Venosa N. Di,
Pistolese M.,
Casanova G.,
Tiravanti E.,
Colantuono G.,
Federici A.,
Paradies G.,
Ruggiero F. M.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4692com
Subject(s) - cardiolipin , melatonin , bioenergetics , mitochondrion , reactive oxygen species , reperfusion injury , mitochondrial ros , medicine , lipid peroxidation , oxidative stress , ischemia , oxidative phosphorylation , chemistry , pharmacology , endocrinology , biology , biochemistry , phospholipid , membrane
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 me‐latonin‐treated ischemic‐reperfused rat heart, various bioenergetic parameters were evaluated such as rates of mitochondrial oxygen consumption, complex I and complex III activity, H 2 O 2 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.—Petrosillo, G., Di Venosa, N., Pistolese, M., Casanova, G., Tiravanti, E., Colantuono, G., Federici, A., Paradies, G., Ruggiero, F. M. Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia‐reperfusion: role of cardiolipin. FASEB J. 20, 269 −276 (2006)