de Souza Elen M, Oliveira Gabriel M, Soeiro Maria de Nazaré C
Lab. Biologia Celular, DUBC, Instituto Oswaldo Cruz, FIOCRUZ, Rio de Janeiro, RJ, Brasil.
Drug Target Insights. 2007;2:61-9. Epub 2007 Mar 5.
Aromatic diamidines have been successfully used to combat a wide range of parasites that cause important human infections. Recently we reported that a N-phenyl-substituted analogue of furamidine (DB569) exerts a micromolar trypanocidal activity against Trypanosoma cruzi in vitro. Since DB569 also reduces the cardiac parasitism and increases the survival rates of T. cruzi-infected mice, our present aim was to analyze the potential protection of DB569 in the development of altered cardiac electrical conduction system during acute and chronic T. cruzi infection. In our experimental model of acute infection (Swiss mice inoculated with Y strain of T. cruzi), the prevailing disorder observed in electrocardiogram (ECG) analyses was sinus bradycardia. This ECG alteration was reverted in acutely infected mice treated with DB569. Interestingly, the DB569 treatment reduced significantly the numbers of CD8(+) T cells in the cardiac infiltration. In addition, the noticed protection of DB569 in the ECG findings of acutely-infected animals was further extended to the chronic infection. Our data suggest that the reversion to and further maintenance of normal ECG profile in the DB569-treated infected animals may be associated with the reduced cardiac CD8(+) lymphocyte infiltration and parasitism that might be ultimately contributing to their increased survival rates.
芳香二脒已成功用于对抗多种导致重要人类感染的寄生虫。最近我们报道，一种呋喃脒的N-苯基取代类似物（DB569）在体外对克氏锥虫具有微摩尔级的杀锥虫活性。由于DB569还能减少心脏寄生虫感染并提高克氏锥虫感染小鼠的存活率，我们目前的目标是分析DB569在急性和慢性克氏锥虫感染期间心脏电传导系统改变发展过程中的潜在保护作用。在我们的急性感染实验模型（接种克氏锥虫Y株的瑞士小鼠）中，心电图（ECG）分析中观察到的主要紊乱是窦性心动过缓。在用DB569治疗的急性感染小鼠中，这种心电图改变得到了逆转。有趣的是，DB569治疗显著减少了心脏浸润中CD8(+) T细胞的数量。此外，DB569在急性感染动物心电图结果中所观察到的保护作用进一步扩展到了慢性感染。我们的数据表明，在接受DB569治疗的感染动物中，心电图恢复正常并进一步维持正常可能与心脏CD8(+)淋巴细胞浸润和寄生虫感染减少有关，这最终可能有助于提高它们的存活率。
