Is Short-term Exercise a Therapeutic Tool for Improvement of Cardioprotection Against DOX-induced Cardiotoxicity? An Experimental Controlled Protocol in Rats
Is Short-term Exercise a Therapeutic Tool for Improvement of Cardioprotection Against DOX-induced Cardiotoxicity? An Experimental Controlled Protocol in Rats
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DOI：
10.7314/apjcp.2012.13.8.4025
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发表时间：
2012-01-01
影响因子：
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通讯作者：
Roshan, Valiollah Dabidi
中科院分区：
文献类型：
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作者：
Ashrafi, Javad;Roshan, Valiollah Dabidi
背景和目的：心脏毒性和氧化应激是阿霉素(DOX)的一种危及生命的副作用。我们研究了短期运动作为治疗工具对改善对DOX诱导的大鼠心脏毒性的心脏保护的效果。方法：体重257+/-28g的Wistar雄性大鼠随机分为6组：(1)对照组+安慰剂(2)对照组+DOX 10 mg·kg(-1)(3)对照组+DOX 20 mg·kg(-1)(4)训练+安慰剂(5)训练+DOX10 mg·kg(-1)(6)训练+DOX 20 mg·kg(-1)。DOX(10和20 mg·kg~(-1))引起心脏毒性。第4、5、6组大鼠进行25~39min的跑台运动。D(-1)和15-17 m in(-1)，5天/周，共3周。耐力训练结束后，1组和4组、2组和5组、3组和6组分别给予生理盐水、DOX 10 mg·kg(-1)和DOX 20 mg·kg(-1)。结果：与C+P组比较，DOX(10和20 mg·kg~(-1))组大鼠血清中MDA和Apelin显著升高，NO升高不明显，而SOD显著降低。与C+P组比较，3周前耐力训练组Apelin、SOD显著升高，NO升高不明显，MDA降低不明显。此外，与C+DOX10和/或C+DOX20组相比，耐力训练和DOX治疗3周后，与C+DOX10和/或C+DOX20组相比，APELIN和SOD显著升高，而丙二醛显著降低。DOX10 mg·kg(-1)组和DOX20 mg·kg(-1)组之间只有丙二醛水平有显著差异。结论：运动预适应可通过抑制心肌组织氧化应激和上调抗氧化剂水平，提高心肌对DOX心脏毒性的耐受性。
Background and Objective: Cardiotoxicity and oxidative stress is a life-threatening side effect of doxorubicin (DOX). We investigate the effects of short-term exercise as therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity in the rat. Methods: Wistar males (weighing 257 +/- 28 g) were divided into six groups: (1) control+placebo (2) control+DOX 10 mg.kg(-1) (3) control+DOX 20mg.kg(-1) (4) training+placebo (5) training+DOX10 mg.kg(-1) (6) training+DOX 20mg.kg(-1). Cardiotoxicity was induced by DOX (10 and 20 mg.kg(-1)). The rats in groups 4, 5 and 6 experienced treadmill running of 25 to 39 min. day(-1) and 15 to 17 m. min(-1), 5 days/wk for 3 wk. At the end of the endurance training program, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, DOX 10 mg.kg(-1) and DOX 20 mg.kg(-1), respectively. Result: DOX administration (10 and 20 mg.kg(-1)) caused significant increase in MDA and Apelin, an insignificant increase in NO and a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment endurance exercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificant decrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOX treatment with 10mg.kg(-1) and 20mg.kg(-1), a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant difference between DOX10 mg.kg(-1) and DOX20 mg.kg(-1) treatments in MDA levels only. Conclusion: Pretreatment exercise may improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and upregulation of antioxidants in heart tissue.