Petrosillo G, Di Venosa N, Pistolese M, Casanova G, Tiravanti E, Colantuono G, Federici A, Paradies G, Ruggiero F M
Department of Biochemistry and Molecular Biology and CNR Institute of Biomembranes and Bioenergetics, University of Bari, Bari Italy.
FASEB J. 2006 Feb;20(2):269-76. doi: 10.1096/fj.05-4692com.
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.
活性氧（ROS）被认为是心肌细胞缺血/再灌注损伤的一个重要因素。线粒体呼吸，主要是在复合体I和III水平，是ROS产生的一个重要来源，因此是心脏再灌注损伤的一个潜在因素。适当的抗氧化策略对于限制这种ROS产生及相关的线粒体功能障碍可能特别有用。褪黑素已被证明能有效预防缺血-再灌注心肌损伤。褪黑素发挥这种心脏保护作用的机制尚未完全明确。在本研究中，我们在Langendorff离体灌注大鼠心脏模型中研究了褪黑素对线粒体生物能量学各种参数的影响。从对照、缺血-再灌注及褪黑素处理的缺血-再灌注大鼠心脏分离出线粒体后，评估了各种生物能量参数，如线粒体氧消耗率、复合体I和复合体III活性、H2O2产生以及脂质过氧化程度、心磷脂含量和心磷脂氧化。我们发现再灌注显著改变了所有这些线粒体参数，而褪黑素处理具有强大的保护作用，可减轻这些改变。这种作用似乎至少部分是由于在ROS攻击下，对在线粒体生物能量学中起关键作用的心磷脂分子的含量和完整性的保护。线粒体功能障碍的保护与心脏缺血后血流动力学功能的改善相关。褪黑素对离体线粒体中复合体I和III以及心磷脂的氧化改变也有强大的保护作用。
