Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and α-tocopherol
Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and α-tocopherol
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DOI：
10.1016/j.etp.2008.04.015
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发表时间：
2008-09-01
影响因子：
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通讯作者：
Nair, Cherupally Krishnan Krishnan
中科院分区：
文献类型：
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作者：
Maliakel, Dani Mathew;Kagiya, Tsutomu V.;Nair, Cherupally Krishnan Krishnan
背景：顺铂是治疗癌症最广泛使用的细胞毒性治疗药物之一。这种药物，在有效的较高剂量下，会引起许多生理不良反应，如肾毒性和遗传毒性。方法：分别腹腔注射顺铂和抗坏血酸单葡萄糖苷（AsAG）或α-生育酚单葡萄糖苷（TMG），观察各组大鼠血清尿素、肌酐水平、肾组织脂质过氧化反应、肾脏抗氧化剂及肾组织病理学改变。对小鼠给予顺铂可诱导明显的肾衰竭，其特征是血清尿素和肌酸酐水平显着增加，以及肾组织结构的严重改变。顺铂还诱导氧化应激，表现为肾组织中脂质过氧化反应增加和还原型谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPx）、超氧化物歧化酶（SOD）和过氧化氢酶水平降低。AsAG或TMG可显著降低顺铂所致的高血肌酐和尿素水平，并可对抗顺铂对氧化应激指标的影响，保护组织免受顺铂所致的脂质过氧化损伤。结论：AsAG或TMG对顺铂所致的小鼠肾损伤具有保护作用。这种保护是通过防止抗氧化状态的下降来介导的。这些结果对AsAG或TMG在人类应用中用于保护免受药物诱导的肾毒性具有意义。(C)2008年Elsevier GmbH。All rights reserved.
Background: Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. This drug, at effective higher doses, causes many physiological adverse effects such as nephrotoxicity and genotoxicity. The toxicity of the drug has been attributed to the induction of oxidative free radicals.Methods: Following intraperitoneal administration of cisplatin and ascorbic acid monoglucoside (AsAG) or alpha-tocopherol monoglucoside (TMG), investigations were conducted on levels of serum urea and creatinine, peroxidation of lipids in renal tissues, renal antioxidants and histopathology of renal tissue.Results: Administration of cisplatin to mice induced a marked renal failure, characterized by significant increase in serum urea and creatinine levels in addition to severe alterations in renal tissue architecture. Cisplatin also induced oxidative stress as indicated by increased lipid peroxidation and decreased levels of reduced glutathione (GSH), glutathione peroxidase (GPx), Superoxide dismutase (SOD) and catalase in renal tissues. Administration of AsAG or TMG markedly reduced the cisplatin-induced higher plasma creatinine and urea levels and counteracted the deleterious effects of cisplatin on oxidative stress markers and protected the tissues from the cisplatin-induced lipid peroxidation.Conclusion: These results indicated that AsAG or TMG has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of AsAG or TMG in human application for protecting against drug-induced nephrotoxicity. (C) 2008 Elsevier GmbH. All rights reserved.