Treatment with benznidazole during the chronic phase of experimental Chagas' disease decreases cardiac alterations
Treatment with benznidazole during the chronic phase of experimental Chagas' disease decreases cardiac alterations
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DOI：
10.1128/aac.49.4.1521-1528.2005
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发表时间：
2005-04-01
影响因子：
4.9
通讯作者：
Soares, MBP
中科院分区：
文献类型：
--
作者：
Garcia, S;Ramos, CO;Soares, MBP
由克氏锥虫感染引起的恰加斯病是拉丁美洲国家因心力衰竭而死亡的主要原因之一。苄硝哒唑是最常用于治疗沙眼衣原体患者的化疗剂，具有高毒性，疗效有限，特别是在疾病的慢性期。在本研究中，我们使用了慢性恰加斯病的小鼠模型，以调查在慢性期对疾病进展的苄硝唑治疗的影响。与未经治疗的查格米病小鼠的心脏相比，苯并咪唑治疗小鼠的心脏具有减少的寄生虫和心肌炎。与健康小鼠相比，两组克氏锥虫感染小鼠的心电图都有显著变化。然而，未治疗的小鼠比苯并咪唑治疗的小鼠具有显著更高的心脏传导障碍，包括心室内传导障碍、房室传导阻滞和期外收缩。血清抗T.克氏抗原（外鞭毛体提取物、P-2 β和转唾液酸酶）以及抗第二细胞外环β（1）-肾上腺素能和M-2-毒蕈碱心脏受体肽的抗体在苯并咪唑处理的小鼠血清中也低于未处理小鼠的血清。这些结果表明，在感染的慢性期用苄硝唑治疗可以预防严重慢性心肌病的发展，尽管缺乏完全的寄生虫根除。此外，我们的数据强调了寄生虫持续存在在慢性恰加斯病发展中的作用，并加强了T。Cruzi消除，以减少或预防严重的胆固醇性心肌病的发展。
Chagas' disease, caused by Trypanosoma cruzi infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of Trypanosoma cruzi-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against T. cruzi antigens (epimastigote extract, P-2 beta, and trans-sialidase) as well as antibodies against peptides of the second extracellular loops beta(1)-adrenergic and M-2-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of T. cruzi elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy.