Bartekova Monika, Barancik Miroslav, Ferenczyova Kristina, Dhalla Naranjan S
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Department of Physiology and Pathophysiology, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research Center, Max Rady College of Medicine, University of Manitoba, Winnipeg, Canada.
Curr Med Chem. 2018 Jan 30;25(3):355-366. doi: 10.2174/0929867324666170608111917.
Ischemia-reperfusion (I/R) injury of the heart as a consequence of myocardial infarction or cardiac surgery represents a serious clinical problem. One of the most prominent mechanisms of I/R injury is the development of oxidative stress in the heart. In this regard, I/R has been shown to enhance the production of reactive oxygen/nitrogen species in the heart which lead to the imbalance between the pro-oxidants and antioxidant capacities of the endogenous radical-scavenging systems.
Increasing the antioxidant capacity of the heart by the administration of exogenous antioxidants is considered beneficial for the heart exposed to I/R. N-acetylcysteine (NAC) and Nmercaptopropionylglycine (MPG) are two sulphur containing amino acid substances, which belong to the broad category of exogenous antioxidants that have been tested for their protective potential in cardiac I/R injury.
Pretreatment of hearts with both NAC and MPG has demonstrated that these agents attenuate the I/R-induced alterations in sarcolemma, sarcoplasmic reticulum, mitochondria and myofibrils in addition to improving cardiac function. While experimental studies have revealed promising data suggesting beneficial effects of NAC and MPG in cardiac I/R injury, the results of clinical trials are not conclusive because both positive and no effects of these substances have been reported on the post-ischemic recovery of heart following cardiac surgery or myocardial infarction.
It is concluded that both NAC and MPG exert beneficial effects in preventing the I/Rinduced injury; however, further studies are needed to establish their effectiveness in reversing the I/R-induced abnormalities in the heart.
心肌梗死或心脏手术后发生的心脏缺血再灌注(I/R)损伤是一个严重的临床问题。I/R损伤最显著的机制之一是心脏中氧化应激的发展。在这方面,I/R已被证明会增强心脏中活性氧/氮物质的产生,这会导致内源性自由基清除系统的促氧化剂和抗氧化能力之间的失衡。
通过给予外源性抗氧化剂来提高心脏的抗氧化能力,被认为对遭受I/R的心脏有益。N-乙酰半胱氨酸(NAC)和N-巯基丙酰甘氨酸(MPG)是两种含硫氨基酸物质,它们属于已被测试其在心脏I/R损伤中保护潜力的外源性抗氧化剂大类。
用NAC和MPG对心脏进行预处理已表明,这些药物除了改善心脏功能外,还能减轻I/R诱导的肌膜、肌浆网、线粒体和肌原纤维的改变。虽然实验研究已揭示出有前景的数据,表明NAC和MPG对心脏I/R损伤有有益作用,但临床试验结果并不确凿,因为这些物质对心脏手术后或心肌梗死后缺血后心脏恢复的影响既有积极的也有无效的报道。
得出结论,NAC和MPG在预防I/R诱导的损伤方面均发挥有益作用;然而,需要进一步研究以确定它们在逆转心脏I/R诱导的异常方面的有效性。