Pretreatment Hepatoprotective Effect of Regular Aerobic Training Against Hepatic Toxicity Induced by Doxorubicin In Rats
Pretreatment Hepatoprotective Effect of Regular Aerobic Training Against Hepatic Toxicity Induced by Doxorubicin In Rats
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DOI：
10.7314/apjcp.2013.14.5.2931
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发表时间：
2013-01-01
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：
Zolfagharzadeh, Fatemeh;Roshan, Valiollah Dabidi
背景：阿霉素是一种蒽环类抗生素，作为一种最有效的抗肿瘤药物，常用于治疗多种癌症。然而，其临床使用与许多健康组织中的毒性作用有关。在这里，我们研究了有规律的有氧运动对急性暴露于DOX诱导的肝毒性大鼠氧化应激的预处理效果。材料与方法：48只Wistar雄性大鼠随机分为对照组和训练组。训练方案为跑台运动，25 ~ 54 min/d，15 ~ 20 m/min，5 d/周，共6周。运动训练结束后，将对照组和训练组大鼠再次随机分为3个亚组：DOX 10 mg/kg、DOX 20 mg/kg和生理盐水。在最后一次运动后24小时进行所有治疗，并在DOX和盐水注射后24小时处死动物。结果：与对照组相比，DOX给药（10和20 mg.kg（-1））导致肝组织中与氧化剂和抗氧化剂相关的生物标志物失衡。与对照+DOX 10 mg/kg组相比，6周的预训练导致一氧化氮（NO）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPX）显著增加。DOX 20 mg/kg给药前训练还可导致NO和SOD显著升高，MDA显著降低。此外，DOX 10 mg/kg和DOX 20 mg/kg处理之间仅MDA水平存在显著差异。结论：本研究的结果表明，有氧运动预处理诱导积极的适应，并对阿霉素（DOX）诱导的肝毒性具有潜在的保护作用，剂量为10和20 mg. kg。
Background: Doxorubicin is an anthracycline antibiotic commonly used to treat a variety of cancers as a most effective antitumor. However, its clinical use is associated with the toxic effects in numerous healthy tissues. Here we investigated the pretreatment effect of regular aerobic exercise on oxidative stress in rats acutely exposed to DOX-induced hepatotoxicity. Materials and Methods: Forty-eight Wistar male rats were randomly divided into 2 groups: control and training. The training protocol included treadmill running between 25 to 54 min/day and 15 to 20m/min, 5 days/week for 6 weeks. At the end of the exercise training protocol, rats from the control and trained groups were again randomly separated into 3 subgroups: DOX10mg/kg, DOX20mg/kg and saline. All treatments were carried 24 h after the last exercise bout and animals were sacrificed 24 h after DOX and saline injections. Results: Administration of DOX (10 and 20 mg.kg(-1)) resulted in imbalance in biomarkers related to oxidants and antioxidants in liver tissue, as compared to control groups. Six weeks of pretreatment training led to a significant increase in nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as compared to the control+DOX 10 mg/kg group. Training before DOX 20 mg/kg administration also led to a significant increase in NO and SOD, and a significant decrease in malondialdehyde (MDA). In addition, there was a significant difference between DOX 10 mg/kg and DOX 20 mg/kg treatments in MDA levels, only. Conclusions: The results of the present study indicate that pretreatment with aerobic exercise induces positive adaptations and has a potential protective effect against doxorubicin (DOX)-induced hepatotoxicity with doses of 10 and 20 mg.kg.