Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Laboratório de Ultraestrutura Celular, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil.
Microbiol Spectr. 2022 Feb 23;10(1):e0185221. doi: 10.1128/spectrum.01852-21. Epub 2022 Feb 9.
Chagas disease (CD), caused by Trypanosoma cruzi, affects approximately 6 to 7 million people in Latin America, with cardiomyopathy being the clinical manifestation most commonly associated with patient death during the acute phase. The etiological treatment of CD is restricted to benznidazole (Bz) and nifurtimox (Nif), which involve long periods of administration, frequent side effects, and low efficacy in the chronic phase. Thus, combined therapies emerge as an important tool in the treatment of CD, allowing the reduction of Bz dose and treatment duration. In this sense, amiodarone (AMD), the most efficient antiarrhythmic drug currently available and prescribed to CD patients, is a potential candidate for combined treatment due to its known trypanocidal activity. However, the efficacy of AMD during the acute phase of CD and its interaction with Bz or Nif are still unknown. In the present study, using a well-established murine model of the acute phase of CD, we observed that the Bz/AMD combination was more effective in reducing the peak parasitemia than both monotherapy treatments. Additionally, the Bz/AMD combination reduced (i) interleukin-6 (IL-6) levels in cardiac tissue, (ii) P-wave duration, and (iii) frequency of arrhythmia in infected animals and (iv) restored gap junction integrity in cardiac tissue. Therefore, our study validates AMD as a promising candidate for combined therapy with Bz, reinforcing the strategy of combined therapy for CD. Chagas disease affects approximately 6 to 7 million people worldwide, with cardiomyopathy being the clinical manifestation that most commonly leads to patient death. The etiological treatment of Chagas disease is limited to drugs (benznidazole and nifurtimox) with relatively high toxicity and therapeutic failures. In this sense, amiodarone, the most effective currently available antiarrhythmic drug prescribed to patients with Chagas disease, is a potential candidate for combined treatment due to its known trypanocidal effect. In the present study, we show that combined treatment with benznidazole and amiodarone improves the trypanocidal effect and reduces cardiac damage in acutely T. cruzi-infected mice.
恰加斯病（CD）由克氏锥虫引起，影响拉丁美洲约 600 至 700 万人，其中心肌病是急性阶段导致患者死亡的最常见临床表现。CD 的病因治疗仅限于苯并咪唑（Bz）和硝呋莫司（Nif），它们的治疗需要长时间进行，且副作用频繁，在慢性阶段疗效较低。因此，联合治疗成为 CD 治疗的重要手段，可以减少 Bz 的剂量和治疗时间。在这方面，胺碘酮（AMD）是目前最有效的抗心律失常药物，也是 CD 患者的常用药物，由于其已知的杀锥虫活性，它是联合治疗的潜在候选药物。然而，AMD 在 CD 的急性阶段的疗效及其与 Bz 或 Nif 的相互作用尚不清楚。在本研究中，我们使用了一种成熟的 CD 急性阶段的小鼠模型，观察到 Bz/AMD 联合治疗比单药治疗更有效地降低峰值寄生虫血症。此外，Bz/AMD 联合治疗降低了（i）心脏组织中白细胞介素-6（IL-6）的水平，（ii）P 波持续时间，（iii）感染动物心律失常的频率，以及（iv）恢复心脏组织中的间隙连接完整性。因此，我们的研究验证了 AMD 作为 Bz 联合治疗的有前途的候选药物，为 CD 的联合治疗策略提供了支持。
