Zaidenberg Anibal, Luong Tai, Lirussi Darío, Bleiz Jorge, Del Buono María Beatriz, Quijano Graciela, Drut Ricardo, Kozubsky Leonora, Marron Adriana, Buschiazzo Héctor
Institute of Paediatric Research (IDIP-CIC), Children's Hospital "Sor María Ludovica", Argentina.
Basic Clin Pharmacol Toxicol. 2006 Apr;98(4):351-6. doi: 10.1111/j.1742-7843.2006.pto_253.x.
We tested trifluralin against Trypanosoma cruzi in a model of chronic Chagas disease in mice. CF1 mice (n=148) were intraperitoneally infected with 10(5) trypomastigotes of T. cruzi, H510C8C3 clone. One hundred mice were partially treated with benznidazole. Mortality was 100% at day 41 in the control group (n=48). At day 90 of the chronic disease (74% survival) mice were divided into three groups and treated orally with trifluralin (50 mg/kg/day, n=26), benznidazole (50 mg/kg/day, n=25) and vehicle (peanut oil; control group, n=23) for 60 days. Electrocardiography (under pentobarbital anaesthesia, 30 mg/kg/dose), serologic immunofluorescence and microstrout were performed at the beginning and at the end of the treatment. Mice were sacrificed at day 10 after treatment; cardiac tissue was studied histopathologically and polymerase chain reaction (PCR) was performed. Spontaneous mortality was 30.43%, 3.85% and 4% in the control, trifluralin and benznidazole groups, respectively (significant survival, P=0.03). Microstrouts were negative in all three groups. Negative immunofluorescence titers were 0%, 16% (P=0.05) and 29% (P<0.02) in the control, trifluralin and benznidazole groups, respectively. The prevailing electrocardiographic disorder was prolongation of the PR interval in the control group, which was not significantly altered in trifluralin- and benznidazole-treated mice, suggesting that trifluralin and benznidazole improve or even stop the damage caused by the disease on the conduction system. Trifluralin- and benznidazole-treated animals showed similar histologic patterns of myocarditis. PCR results were negative for benznidazole and trifluralin (100% and 70.8%, respectively). These results show the therapeutic potential of trifluralin in the treatment of chronic Chagas disease.
我们在小鼠慢性恰加斯病模型中测试了氟乐灵对克氏锥虫的作用。CF1小鼠（n = 148）经腹腔注射感染了10⁵个克氏锥虫H510C8C3克隆的锥鞭毛体。100只小鼠用苯硝唑进行了部分治疗。对照组（n = 48）在第41天的死亡率为100%。在慢性疾病的第90天（存活率74%），小鼠被分为三组，分别口服氟乐灵（50 mg/kg/天，n = 26）、苯硝唑（50 mg/kg/天，n = 25）和赋形剂（花生油；对照组，n = 23），持续60天。在治疗开始和结束时进行心电图检查（在戊巴比妥麻醉下，30 mg/kg/剂量）、血清学免疫荧光检查和微型芽殖检查。治疗后第10天处死小鼠；对心脏组织进行组织病理学研究并进行聚合酶链反应（PCR）。对照组、氟乐灵组和苯硝唑组的自然死亡率分别为30.43%、3.85%和4%（存活率有显著差异，P = 0.03）。三组的微型芽殖检查均为阴性。对照组、氟乐灵组和苯硝唑组的阴性免疫荧光滴度分别为0%、16%（P = 0.05）和29%（P < 0.02）。对照组中主要的心电图紊乱是PR间期延长，在氟乐灵和苯硝唑治疗的小鼠中没有明显改变，这表明氟乐灵和苯硝唑改善甚至阻止了疾病对传导系统造成的损害。氟乐灵和苯硝唑治疗的动物表现出相似的心肌炎组织学模式。苯硝唑和氟乐灵的PCR结果均为阴性（分别为100%和70.8%）。这些结果显示了氟乐灵在治疗慢性恰加斯病方面的治疗潜力。
