REQUIMTE (Rede de Química e Tecnologia), Laboratório de Toxicologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto , Porto, Portugal.
Chem Res Toxicol. 2013 Sep 16;26(9):1285-311. doi: 10.1021/tx400130v. Epub 2013 Aug 23.
The heart is a target organ for oxidative stress-related injuries. Because of its very high energetic metabolic demand, the heart has the highest rate of production of reactive oxygen species, namely, hydrogen peroxide (H2O2), per gram of tissue. Additionally, the heart has lower levels of antioxidants and total activity of antioxidant enzymes when compared to other organs. Furthermore, drugs that have relevant antioxidant activity and that are used in the treatment of oxidative stress related cardiac diseases demonstrate better clinical cardiac outcomes than other drugs with similar receptor affinity but with no antioxidant activity. Several xenobiotics particularly target the heart and promote toxicity. Anticancer drugs, like anthracyclines, cyclophosphamide, mitoxantrone, and more recently tyrosine kinase targeting drugs, are well-known cardiac toxicants whose therapeutic application has been associated to a high prevalence of heart failure. High levels of catecholamines or drugs of abuse, namely, amphetamines, cocaine, and even the consumption of alcohol for long periods of time, are linked to cardiovascular abnormalities. Oxidative stress may be one common link for the cardiac toxicity elicited by these compounds. We aim to revise the mechanisms involved in cardiac lesions caused by the above-mentioned substances specially focusing in oxidative stress related pathways. Oxidative stress biomarkers can be useful in the early recognition of cardiotoxicity in patients treated with these drugs and aid to minimize the setting of cardiac irreversible events.
心脏是氧化应激相关损伤的靶器官。由于其极高的能量代谢需求，心脏产生的活性氧种类（即过氧化氢 (H2O2)）的速率在每克组织中最高。此外，与其他器官相比，心脏的抗氧化剂水平和总抗氧化酶活性都较低。此外，具有相关抗氧化活性并用于治疗氧化应激相关心脏疾病的药物比其他具有相似受体亲和力但无抗氧化活性的药物具有更好的临床心脏结局。一些外源性物质特别针对心脏并促进毒性。抗癌药物，如蒽环类药物、环磷酰胺、米托蒽醌，以及最近的酪氨酸激酶靶向药物，都是众所周知的心脏毒物，其治疗应用与心力衰竭的高患病率有关。儿茶酚胺水平升高或滥用药物，如安非他命、可卡因，甚至长期饮酒，都与心血管异常有关。氧化应激可能是这些化合物引起心脏毒性的一个共同途径。我们旨在修订由上述物质引起的心脏损伤的相关机制，特别是专注于与氧化应激相关的途径。氧化应激生物标志物可用于早期识别接受这些药物治疗的患者的心脏毒性，并有助于最小化心脏不可逆事件的发生。
