Vitamin C Protects Against Cisplatin-Induced Nephrotoxicity and Damage Without Reducing Its Effectiveness in C57BL/6 Mice Xenografted With Lewis Lung Carcinoma
Vitamin C Protects Against Cisplatin-Induced Nephrotoxicity and Damage Without Reducing Its Effectiveness in C57BL/6 Mice Xenografted With Lewis Lung Carcinoma
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DOI：
10.1080/01635581.2014.948211
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发表时间：
2014-10-03
影响因子：
2.9
通讯作者：
Hu, Miao-Lin
中科院分区：
文献类型：
--
作者：
Chen, Ming-Feng;Yang, Chih-Min;Hu, Miao-Lin
维生素C（vit C）已被证明可以减少健康大鼠和小鼠中顺铂（CP）诱导的肾毒性和氧化损伤。然而，很少有人知道维生素C是否具有类似的作用，并加强CP在荷瘤小鼠中的抗癌作用。在本文中，将C57 BL/6小鼠植入（s.c.）小鼠刘易斯肺癌（LLC）模型，腹腔注射CP（5 mg/kg），同时腹腔注射低剂量（200 mg/kg）和高剂量（1000 mg/kg）VitC，每周2次，共28天。结果显示，单独的维生素C或CP处理显著抑制肿瘤生长，尽管与单独的CP处理相比，维生素C与CP组合没有进一步抑制肿瘤生长。此外，CP还可引起肾毒性和氧化损伤，表现为血浆尿素氮和肌酐水平升高，肝、肾脂质过氧化和羰基化水平升高，GSH/GSSG比值降低。维生素C可明显逆转CP引起的这些不良反应，且大多数作用呈剂量依赖性。总的来说，我们得出结论，维生素C可以防止CP诱导的肾毒性和损伤，而不会降低CP在LLC小鼠中的有效性。
Vitamin C (vit C) has been shown to diminish cisplatin (CP)-induced nephrotoxicity and oxidative damage in healthy rats and mice. However, little is known whether vit C has similar actions and enhances the anticancer effect of CP in tumor-bearing mice. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma (LLC) for 9days before intraperitoneal administration with CP (5mg/kg) in the presence or absence of low- (200mg/kg) and high- (1000mg/kg) dose vit C twice a week for an additional 28days. Results reveal that vit C or CP treatment alone significantly inhibited tumor growth, although vit C in combination with CP did not further inhibit tumor growth, as compared to CP treatment alone. In addition, CP significantly induced nephrotoxicity and oxidative damage, as evidenced by increased plasma levels of blood urea nitrogen and creatinine as well as levels of lipid peroxidation and carbonyls, decreased ratios of GSH/GSSG in liver and kidney. Vit C significantly reversed these undesirable side effects induced by CP, and most of these actions of vit C were dose-dependent. Overall, we conclude that vit C can protect against CP-induced nephrotoxicity and damage without reducing CP's effectiveness in LLC-bearing mice.