Department of Biochemistry, Faculty of Life Sciences, A M University, Aligarh, UP, India.
J Clin Pharm Ther. 2012 Feb;37(1):22-6. doi: 10.1111/j.1365-2710.2010.01237.x. Epub 2011 Jan 4.
Reactive oxygen/nitrogen species generated by antineoplastic agents are prime suspects for the toxic side-effects of acute or chronic chemotherapy. The present study was undertaken to test whether vitamins C and E (VCE) supplementation protect against some of the harmful effects of commonly used anticancer drugs in breast-cancer patients.
In a randomized 5-month study, the activity of various antioxidant enzymes (superoxide dismutase, catalase, glutathione-S-transferase and glutathione reductase) and the levels of malondialdehyde and reduced glutathione were measured in forty untreated breast-cancer patients (stage II) and compared with those of healthy controls. The degree of DNA damage was also assessed in the peripheral lymphocytes of the patients by alkaline single cell gel electrophoresis. The untreated patients were then randomly assigned to either treatment with chemotherapy alone (5-fluorouracil 500 mg/m(2) i.v. day 1, doxorubicin 50 mg/m(2) i.v. day 1 and cyclophosphamide 500 mg/m(2) i.v. day 1, every 3 weeks for six cycles) or to the same chemotherapy regimen supplemented with VCE (vitamin C 500 mg tablet and vitamin E 400 mg gelatin capsule). On completion of the treatments, both the groups were studied again for the levels of the markers measured prior to treatment.
The untreated group showed significantly lower levels of antioxidant enzymes (P < 0·001) and reduced glutathione (P < 0·001), and more extensive lipid peroxidation (P < 0·001) and DNA damage than healthy controls. Similar but less pronounced patterns were observed in the patients receiving chemotherapy alone. The group of patients receiving VCE supplementation had all the marker levels moving towards normal values. Activities of superoxide dismutase, catalase, glutathione-S-transferase and glutathione reductase, and the levels of reduced glutathione were significantly increased (P < 0·01) while, the levels of malondialdehyde and DNA damage were significantly (P < 0·01) reduced in the VCE supplemented group relative to those of patients receiving chemotherapy alone as well as relative to the pretreatment levels.
Co-administration of VCE restored antioxidant status, lowered by the presence of breast-cancer and chemotherapy. DNA damage was also reduced by VCE. The results suggest that VCE should be useful in protecting against chemotherapy-related side-effects and a randomized control trial to evaluate the effectiveness of VCE in breast-cancer patients using clinical outcomes would be appropriate.
抗肿瘤药物产生的活性氧/氮物种是急性或慢性化疗毒性副作用的主要嫌疑犯。本研究旨在测试维生素 C 和 E（VCE）补充剂是否能预防乳腺癌患者常用抗癌药物的一些有害作用。
在一项随机的 5 个月研究中，测量了 40 例未经治疗的乳腺癌患者（II 期）和健康对照组的各种抗氧化酶（超氧化物歧化酶、过氧化氢酶、谷胱甘肽-S-转移酶和谷胱甘肽还原酶）的活性以及丙二醛和还原型谷胱甘肽的水平。还通过碱性单细胞凝胶电泳评估了患者外周淋巴细胞的 DNA 损伤程度。然后，未经治疗的患者被随机分配接受单纯化疗（5-氟尿嘧啶 500 mg/m²静脉注射第 1 天，阿霉素 50 mg/m²静脉注射第 1 天，环磷酰胺 500 mg/m²静脉注射第 1 天，每 3 周 6 个周期）或相同的化疗方案加用 VCE（维生素 C 500 mg 片剂和维生素 E 400 mg 明胶胶囊）。治疗完成后，再次测量两组治疗前测量的标志物水平。
未经治疗的组显示出明显较低的抗氧化酶水平（P < 0.001）和还原型谷胱甘肽水平（P < 0.001），脂质过氧化作用（P < 0.001）和 DNA 损伤更为广泛，明显高于健康对照组。单独接受化疗的患者也观察到类似但程度较轻的模式。接受 VCE 补充的患者组所有标志物水平均向正常值移动。超氧化物歧化酶、过氧化氢酶、谷胱甘肽-S-转移酶和谷胱甘肽还原酶的活性以及还原型谷胱甘肽的水平显著增加（P < 0.01），而丙二醛和 DNA 损伤的水平则显著降低（P < 0.01），与单独接受化疗的患者以及与治疗前的水平相比。
VCE 的联合使用恢复了由乳腺癌和化疗引起的抗氧化状态。VCE 还降低了 DNA 损伤。结果表明，VCE 有助于预防化疗相关的副作用，使用临床结局评估 VCE 在乳腺癌患者中的有效性的随机对照试验将是合适的。
