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基于铂的化合物与老年人心血管毒性风险:抗氧化剂在化学预防中的作用。

Platinum-based compounds and risk for cardiovascular toxicity in the elderly: role of the antioxidants in chemoprevention.

机构信息

Department of Laboratory Medicine & Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy.

出版信息

Rejuvenation Res. 2011 Jun;14(3):293-308. doi: 10.1089/rej.2010.1141. Epub 2011 May 19.

DOI:10.1089/rej.2010.1141
PMID:21595514
Abstract

Cancer in elderly patients is an increasingly common problem. Older patients have more co-morbidity, therefore the toxic effects of chemotherapy treatment are less tolerable compared to younger patients. Platinum-based compounds (PBCs) are commonly used cytotoxic agents in the treatment of several solid tumors; however, their application is still limited in elderly patients, due to the risks in cardiovascular toxicity. The increased risk for myocardial ischemia, stroke, and vascular thrombosis linked with PBCs treatment is mainly due to reactive oxygen species (ROS) production and the subsequent induction of oxidative stress and switch to a prothrombotic condition. Recently, studies have shown a different genetic susceptibility in cardiovascular toxicity induced by therapy with PBCs. Antioxidants, such as vitamin E, selenium, lycopene, melatonin, and resveratrol, have been implicated in cancer treatment by their property to suppress the oxidant injury. Resveratrol, especially, has been shown to increase the antineoplastic activity of cisplatin. In addition, resveratrol's ability to activate the sirtuin1 (SIRT1) pathway has been heavily implicated in the mechanisms controlling longevity and quality of life in the aged population. This article reviews the current state of treatment with PBCs and their associated risk for cardiovascular disease. It discusses the most powerful antioxidant supplementation options as a possible strategy to reduce the cardiovascular toxicity effects of chemotherapy in the elderly.

摘要

老年癌症患者的数量日益增加。老年患者合并症较多,因此与年轻患者相比,他们对化疗治疗的毒副作用的耐受性更差。铂类化合物(PBCs)是几种实体瘤治疗中常用的细胞毒性药物;然而,由于心血管毒性的风险,它们在老年患者中的应用仍然有限。PBCs 治疗引起的心肌缺血、中风和血管血栓形成风险增加,主要是由于活性氧(ROS)的产生,以及随后诱导的氧化应激和向促血栓形成状态的转变。最近的研究表明,PBCs 治疗引起的心血管毒性存在不同的遗传易感性。抗氧化剂,如维生素 E、硒、番茄红素、褪黑素和白藜芦醇,因其抑制氧化剂损伤的特性而被认为具有抗癌作用。白藜芦醇,特别是,已被证明可以增加顺铂的抗肿瘤活性。此外,白藜芦醇激活沉默信息调节因子 1(SIRT1)途径的能力与控制老年人群寿命和生活质量的机制密切相关。本文综述了 PBCs 的治疗现状及其与心血管疾病的相关风险。它讨论了作为降低老年人化疗心血管毒性的可能策略的最有效的抗氧化补充剂选择。

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