Effect of alprazolam on anxiety and cardiomyopathy induced by doxorubicin in mice
Effect of alprazolam on anxiety and cardiomyopathy induced by doxorubicin in mice
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DOI：
10.1111/j.1472-8206.2011.00925.x
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发表时间：
2012-06-01
影响因子：
2.9
通讯作者：
Vohora, Divya
中科院分区：
文献类型：
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作者：
Anwar, Md Jamir;Pillai, Krishna K.;Vohora, Divya
心力衰竭（HF）和/或心肌梗死（MI）后的焦虑可阻碍恢复，并构成进一步心脏事件的主要风险因素。本研究的目的是评估小鼠阿霉素（DOX）诱导的心肌病（HF的啮齿动物模型）后的焦虑。此外，该研究还研究了阿普唑仑对该模型中焦虑和心肌病的影响。这项研究是在瑞士白化病小鼠中进行的。DOX以10 mg/kg的剂量静脉内使用。阿普唑仑以0.5、1和2 mg/kg的剂量口服给药，持续DOX前7天和DOX后7天。在第8天和第14天使用高架十字迷宫和Vogels冲突测试测量焦虑。第14天测定血清乳酸脱氢酶（LDH）。然后处死小鼠，解剖出心脏，用于硫代巴比妥酸反应物质的估计和透射电子显微镜（TEM）研究。我们的研究结果表明，DOX给药诱导小鼠心肌病。这通过血清LDH和组织丙二醛（MDA）增加得到证实，并通过TEM研究得到证实。阿普唑仑治疗14天剂量依赖性逆转DOX诱导的LDH和MDA的增加以及TEM研究中DOX诱导的形态学改变。此外，阿普唑仑还逆转了DOX在两项焦虑测试中诱导的焦虑样作用。因此，阿普唑仑似乎是缓解MI或HF患者焦虑的良好候选药物。
Anxiety following heart failure (HF) and/or myocardial infarction (MI) can impede recovery and constitute a major risk factor for further cardiac events. The present study was aimed to evaluate anxiety following doxorubicin (DOX)-induced cardiomyopathy, a rodent model for HF, in mice. Furthermore, the study investigated the effect of alprazolam on anxiety and cardiomyopathy in this model. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg i.v. Alprazolam was administered at doses of 0.5, 1 and 2 mg/kg po for 7 days pre- and 7 days post-DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogels conflict test. On 14th day, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and hearts were dissected out for estimation of thiobarbituric acid reactive substance and Transmission Electron Microscopy (TEM) studies. Our results showed that DOX administration induced cardiomyopathy in mice. This was evidenced by an increased serum LDH and tissue malondialdehyde (MDA) and was confirmed by TEM studies. Alprazolam treatment for 14 days dose dependently reversed DOX-induced increase in LDH and MDA as well as the morphological alterations induced by DOX in TEM studies. Furthermore, alprazolam also reversed the anxiety-like effects induced by DOX in both the tests for anxiety. Thus, alprazolam appears to be a good candidate for alleviating anxiety in patients following MI or HF.