Strauss Mariana, Lo Presti M Silvina, Bazán Paula Carolina, Baez Alejandra, Fauro Romina, Esteves Blanca, Sanchez Negrete Olga, Cremonezzi David, Paglini-Oliva Patricia A, Rivarola H Walter
Cátedra de Física Biomédica, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, Santa Rosa 1085, Córdoba, Argentina.
Parasitol Int. 2013 Jun;62(3):293-9. doi: 10.1016/j.parint.2013.02.004. Epub 2013 Mar 14.
Alternative strategies are being designed to identify candidates among drugs already available on the market that could be used in combination to improve the efficacy of Chagas disease treatment. This work evaluates the effect of the association of clomipramine (CLO) with benznidazole (BZN) for the treatment of experimental Chagas disease in the acute stage, in Swiss albino mice infected with Trypanosoma cruzi Tulahuen strain. Infected mice were treated with CLO 5mg/kg/day and BZN 50 and 100mg/kg/day, each separately or together. Efficacy of the treatment was evaluated through parasitemia, survival, electrocardiography, histopathological studies, serological and PCR assays at 90 days post-infection (dpi). All treatments significantly (P<0.05) reduced mortality and decreased parasitemia. Histopathological analysis of liver and kidneys of mice treated with CLO and the drug combination showed less injury than mice treated only with BZN. The lower dose of BZN (50mg/kg/day) combined with CLO showed the same efficacy as the habitual dose of BZN (100mg/kg/day) combined with CLO. The therapeutic results from the combination of BZN with CLO presented lesser side effects than the treatment with BZN.
正在设计替代策略，以在市场上已有的药物中识别出可以联合使用以提高恰加斯病治疗效果的候选药物。这项研究评估了氯米帕明（CLO）与苯硝唑（BZN）联合用药对感染克氏锥虫图拉洪株的瑞士白化小鼠急性期实验性恰加斯病的治疗效果。感染小鼠分别或联合接受5mg/kg/天的CLO以及50和100mg/kg/天的BZN治疗。在感染后90天（dpi），通过寄生虫血症、存活率、心电图、组织病理学研究、血清学和PCR检测评估治疗效果。所有治疗均显著（P<0.05）降低了死亡率并减少了寄生虫血症。对接受CLO和联合用药治疗的小鼠的肝脏和肾脏进行组织病理学分析，结果显示其损伤程度低于仅接受BZN治疗的小鼠。较低剂量的BZN（50mg/kg/天）与CLO联合使用显示出与习惯剂量的BZN（100mg/kg/天）与CLO联合使用相同的疗效。BZN与CLO联合治疗的结果显示，其副作用比BZN单独治疗更少。
