Lillo-Moya José, Rojas-Solé Catalina, Muñoz-Salamanca Diego, Panieri Emiliano, Saso Luciano, Rodrigo Ramón
Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago 8380000, Chile.
Department of Physiology and Pharmacology "Vittorio Erspamer", Faculty of Pharmacy and Medicine Sapienza University, P.le Aldo Moro 5, 00185 Rome, Italy.
Antioxidants (Basel). 2021 Apr 25;10(5):667. doi: 10.3390/antiox10050667.
Ischemic heart disease is a leading cause of death worldwide. Primarily, ischemia causes decreased oxygen supply, resulting in damage of the cardiac tissue. Naturally, reoxygenation has been recognized as the treatment of choice to recover blood flow through primary percutaneous coronary intervention. This treatment is the gold standard therapy to restore blood flow, but paradoxically it can also induce tissue injury. A number of different studies in animal models of acute myocardial infarction (AMI) suggest that ischemia-reperfusion injury (IRI) accounts for up to 50% of the final myocardial infarct size. Oxidative stress plays a critical role in the pathological process. Iron is an essential mineral required for a variety of vital biological functions but also has potentially toxic effects. A detrimental process induced by free iron is ferroptosis, a non-apoptotic type of programmed cell death. Accordingly, efforts to prevent ferroptosis in pathological settings have focused on the use of radical trapping antioxidants (RTAs), such as liproxstatin-1 (Lip-1). Hence, it is necessary to develop novel strategies to prevent cardiac IRI, thus improving the clinical outcome in patients with ischemic heart disease. The present review analyses the role of ferroptosis inhibition to prevent heart IRI, with special reference to Lip-1 as a promising drug in this clinicopathological context.
缺血性心脏病是全球主要的死亡原因。主要地，局部缺血导致氧气供应减少，从而造成心脏组织损伤。自然而然地，再灌注疗法已被公认为是通过直接经皮冠状动脉介入术恢复血流的首选治疗方法。这种治疗是恢复血流的金标准疗法，但矛盾的是，它也会诱发组织损伤。在急性心肌梗死（AMI）动物模型中进行的多项不同研究表明，缺血再灌注损伤（IRI）占最终心肌梗死面积的50%。氧化应激在这一病理过程中起关键作用。铁是多种重要生物学功能所必需的矿物质，但也具有潜在的毒性作用。游离铁诱导的一个有害过程是铁死亡，这是一种非凋亡性的程序性细胞死亡。因此，在病理情况下预防铁死亡的努力主要集中在使用自由基捕获抗氧化剂（RTA），如脂氧素他汀-1（Lip-1）。因此，有必要开发新的策略来预防心脏IRI，从而改善缺血性心脏病患者的临床结局。本综述分析了抑制铁死亡在预防心脏IRI中的作用，特别提及Lip-1作为在这种临床病理背景下有前景的药物。
