Aluise Christopher D, St Clair Daret, Vore Mary, Butterfield D Allan
Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506-0055, USA.
Cancer Lett. 2009 Sep 8;282(1):25-9. doi: 10.1016/j.canlet.2009.02.047. Epub 2009 Apr 1.
Adriamycin (ADR) is a common chemotherapeutic known to generate significant amounts of reactive oxygen species (ROS). Although ROS generation is one of several means by which ADR attacks cancerous tissues, oxidative stress-related toxicity has been documented in several non-targeted organs as a result of anthracycline chemotherapy. Oxidative damage to tissues has been shown in the past to be minimized with co-administration of various antioxidants. Gamma-glutamylcysteine ethyl ester (GCEE) is an antioxidant and precursor to glutathione that has been shown to successfully defend brain against ADR-induced oxidative stress. The current study shows ADR in vivo also causes oxidative stress in plasma in the form of protein oxidation [indexed by protein carbonyls and protein bound 3-nitrotyrosine] and lipid peroxidation [indexed by protein-bound-4-hydroxynonenal]. All three markers of oxidative stress are significantly suppressed with in vivo co-administration of GCEE. This work further supports the concept that administration of GCEE can protect patients undergoing anthracycline chemotherapy from non-targeted oxidative damage.
阿霉素(ADR)是一种常见的化疗药物,已知会产生大量活性氧(ROS)。虽然ROS的产生是ADR攻击癌组织的几种方式之一,但由于蒽环类化疗,氧化应激相关毒性已在多个非靶器官中得到记录。过去已表明,通过联合使用各种抗氧化剂可将对组织的氧化损伤降至最低。γ-谷氨酰半胱氨酸乙酯(GCEE)是一种抗氧化剂,也是谷胱甘肽的前体,已被证明能成功保护大脑免受ADR诱导的氧化应激。目前的研究表明,ADR在体内还会以蛋白质氧化[以蛋白质羰基和蛋白质结合的3-硝基酪氨酸为指标]和脂质过氧化[以蛋白质结合的4-羟基壬烯醛为指标]的形式在血浆中引起氧化应激。体内联合使用GCEE可显著抑制所有三种氧化应激标志物。这项工作进一步支持了GCEE给药可保护接受蒽环类化疗的患者免受非靶向氧化损伤这一概念。