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阿托伐他汀对阿霉素诱导的小鼠心脏毒性和睾丸毒性的保护作用。

Protective role of atorvastatin against doxorubicin-induced cardiotoxicity and testicular toxicity in mice.

机构信息

Department of Toxicology, NCER&D, Piramal Healthcare Limited, Goregaon East, Mumbai, Maharashtra, India.

出版信息

J Physiol Biochem. 2013 Sep;69(3):513-25. doi: 10.1007/s13105-013-0240-0. Epub 2013 Feb 6.

Abstract

Doxorubicin (DOX), a potent chemotherapeutic agent, is widely used for the treatment of various malignancies. However, its clinical uses are limited due to its dose-dependent adverse effects particularly cardiac and testicular toxicities. DOX-induced toxicity is mainly due to the induction of oxidative stress. Atorvastatin (ATV), a 3-hydroxy 3-methyl glutaryl coenzyme A reductase inhibitor, with lipid-lowering activity, acts as an antioxidant at lower doses. It possesses pleiotropic effects independent of cholesterol-lowering property usually shown at lower doses, which include antioxidant and anti-inflammatory activities. The present study was aimed to investigate the possible protection exerted by atorvastatin against oxidative stress and DNA damage induced by DOX in the heart and testes of mice. The protective role of ATV in the heart and testes of DOX-treated mice was evident from the amelioration of oxidative stress, DNA and cellular damage. The present study clearly indicates that ATV offers a significant protection against DOX-induced oxidative stress and DNA damage in the heart and testes of mice.

摘要

多柔比星(DOX)是一种有效的化疗药物,广泛用于治疗各种恶性肿瘤。然而,由于其剂量依赖性的不良反应,特别是心脏毒性和睾丸毒性,其临床应用受到限制。DOX 诱导的毒性主要是由于氧化应激的诱导。阿托伐他汀(ATV)是一种 3-羟基-3-甲基戊二酰辅酶 A 还原酶抑制剂,具有降脂活性,在较低剂量下作为抗氧化剂发挥作用。它具有独立于降脂作用的多效作用,通常在较低剂量下表现出抗氧化和抗炎作用。本研究旨在探讨阿托伐他汀对 DOX 诱导的心脏和睾丸氧化应激和 DNA 损伤的可能保护作用。阿托伐他汀在 DOX 处理的小鼠心脏和睾丸中的保护作用表现在氧化应激、DNA 和细胞损伤的改善上。本研究清楚地表明,阿托伐他汀对 DOX 诱导的心脏和睾丸氧化应激和 DNA 损伤具有显著的保护作用。

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