Laboratory of Pathophysiology and Free Radicals, Department of General Pathology-Center of Biological Science, State University of Londrina, Londrina, PR 86051-990, Brazil.
Breast Cancer Res Treat. 2012 May;133(1):89-97. doi: 10.1007/s10549-011-1693-x. Epub 2011 Aug 3.
Several adverse effects of chemotherapy treatments have been described, and most of these effects are associated with direct interactions between blood cells and indirect effects generated during the oxidative metabolism of antineoplastic drugs. In this study we evaluated the oxidative systemic status and hematological profiles of breast cancer patients with advanced ductal infiltrative carcinoma treated with doxorubicin (DOX) or paclitaxel (PTX) within 1 h after chemotherapy. Blood analyses included evaluation of hemogram, pro-oxidative markers, and antioxidant status. The results showed that advanced breast cancer diseased (AD) patients without previous chemotherapy presented anemia and high oxidative stress status characterized by elevated levels of lipid peroxidation and nitric oxide, and reduced catalase activity when compared with controls. DOX-treated patients exhibited increased anemia and reduced antioxidant status, which was revealed by decreases in reduced glutathione levels and the total antioxidant capacity of plasma; however, these changes did not lead to further increases in lipid peroxidation or carbonyl proteins when compared with the AD group. PTX-treated patients also showed increased anemia, lactate dehydrogenase leakage, and enhanced lipid peroxidation. These data reveal for the first time that patients subjected to chemotherapy with DOX or PTX present immediate systemic oxidative stress and red blood cell oxidative injury with anemia development. These findings provide a new perspective on the systemic redox state of AD and patients subjected to chemotherapy regarding oxidative stress enhancement and its possible involvement in the aggravation of chronic anemia.
已经描述了几种化疗治疗的不良反应，其中大多数与血细胞之间的直接相互作用以及抗肿瘤药物氧化代谢过程中产生的间接作用有关。在这项研究中，我们评估了在化疗后 1 小时内接受阿霉素（DOX）或紫杉醇（PTX）治疗的晚期导管浸润性乳腺癌患者的全身氧化状态和血液学特征。血液分析包括评估血象、促氧化剂标志物和抗氧化状态。结果表明，与对照组相比，未经化疗的晚期乳腺癌患者（AD）表现出贫血和高氧化应激状态，特征为脂质过氧化和一氧化氮水平升高，过氧化氢酶活性降低。与 AD 组相比，DOX 治疗组患者的贫血和抗氧化状态进一步降低，这表现为还原型谷胱甘肽水平和血浆总抗氧化能力降低；然而，这些变化并没有导致脂质过氧化或羰基蛋白进一步增加。PTX 治疗组患者也表现出贫血、乳酸脱氢酶漏出和脂质过氧化增强。这些数据首次表明，接受 DOX 或 PTX 化疗的患者会立即出现全身氧化应激和红细胞氧化损伤，导致贫血发生。这些发现为 AD 患者和接受化疗的患者的全身氧化还原状态提供了一个新的视角，即氧化应激增强及其可能在慢性贫血加重中的作用。
