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重组人促红细胞生成素对丝裂霉素C诱导的大鼠肾脏和心脏组织氧化应激及遗传毒性的影响。

Effect of recombinant human erythropoietin on mitomycin C-induced oxidative stress and genotoxicity in rat kidney and heart tissues.

作者信息

Rjiba-Touati K, Ayed-Boussema I, Guedri Y, Achour A, Bacha H, Abid-Essefi S

机构信息

Laboratory of Research on Biologically Compatible Compounds, Faculty of Dentistry, Monastir, Tunisia.

Department of Nephrology, Dialysis and Transplant, University Hospital of Sahloul, Sousse, Tunisia.

出版信息

Hum Exp Toxicol. 2016 Jan;35(1):53-62. doi: 10.1177/0960327115577521. Epub 2015 Mar 2.

Abstract

Mitomycin C (MMC) is an antineoplastic agent used for the treatment of several human malignancies. Nevertheless, the prolonged use of the drug may result in a serious heart and kidney injuries. Recombinant human erythropoietin (rhEPO) has recently been shown to exert an important cytoprotective effect in experimental brain injury and ischemic acute renal failure. The aim of the present work is to investigate the cardioprotective and renoprotective effects of rhEPO against MMC-induced oxidative damage and genotoxicity. Our results showed that MMC induced oxidative stress and DNA damage. rhEPO administration in any treatment conditions decreased oxidative damage induced by MMC. It reduced malondialdehyde and protein carbonyl levels. rhEPO ameliorated reduced glutathione plus oxidized glutathione modulation and the increased catalase activity after MMC treatment. Furthermore, rhEPO restored DNA damage caused by MMC. We concluded that rhEPO administration especially in pretreatment condition protected rats against MMC-induced heart and renal oxidative stress and genotoxicity.

摘要

丝裂霉素C(MMC)是一种用于治疗多种人类恶性肿瘤的抗肿瘤药物。然而,长期使用该药物可能会导致严重的心脏和肾脏损伤。重组人促红细胞生成素(rhEPO)最近已被证明在实验性脑损伤和缺血性急性肾衰竭中发挥重要的细胞保护作用。本研究的目的是探讨rhEPO对MMC诱导的氧化损伤和遗传毒性的心脏保护和肾脏保护作用。我们的结果表明,MMC诱导氧化应激和DNA损伤。在任何治疗条件下给予rhEPO均可降低MMC诱导的氧化损伤。它降低了丙二醛和蛋白质羰基水平。rhEPO改善了MMC处理后还原型谷胱甘肽加氧化型谷胱甘肽的调节以及过氧化氢酶活性的增加。此外,rhEPO恢复了MMC引起的DNA损伤。我们得出结论,尤其是在预处理条件下给予rhEPO可保护大鼠免受MMC诱导的心脏和肾脏氧化应激及遗传毒性。

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