Institute of Parasitology, Vetsuisse Faculty, University of Berne, Länggass-Strasse 122, CH-3012 Berne, Switzerland.
Exp Parasitol. 2011 Oct;129(2):95-100. doi: 10.1016/j.exppara.2011.07.010. Epub 2011 Jul 22.
The cationic arylimidamide DB750 and the thiazolide nitazoxanide had been shown earlier to be effective against Neospora caninum tachyzoites in vitro with an IC(50) of 160nM and 4.23μM, respectively. In this study, we have investigated the effects of DB750 and nitazoxanide treatments of experimentally infected Balb/c mice, by applying the drugs either through the oral or the intraperitoneal route. In experiment 1, administration of DB750 (2mg/kg/day) and nitazoxanide (150mg/kg/day) started already 3 days prior to experimental infection of mice with 2×10(6) tachyzoites. Following infection, the drugs were further administrated daily for a period of 2 weeks, either orally or intraperitoneally. Intraperitoneal injection of DB750 was well tolerated by the mice, but treatment with nitazoxanide resulted in death of all mice within 3 days. Upon intraperitoneal application of DB750, the cerebral parasite load was significantly reduced compared to all other groups, while oral application of DB750 and nitazoxanide were not as effective, and resulted in significant weight loss. In experiment 2, mice were infected with 2×10(6) tachyzoites and at 2 weeks post-infection, DB750 (2mg/kg/day) was applied by intraperitoneal injections for 14 days. In the DB750-treated group, only 2 out of 12 mice succumbed to infection, compared to 7 out of 12 mice in the placebo-group. DB750 treatment also resulted in significantly reduced cerebral parasite burden, and reduced numbers of viable tachyzoites. Our data suggest that DB750 exerted its activity also after crossing the blood-brain barrier, and that this class of compounds could be promising for the control of N. caninum-associated disease.
先前的研究表明，阳离子芳基脒 DB750 和噻唑烷酮硝唑尼特对体外培养的刚地弓形虫速殖子具有抑制活性，其半数抑制浓度（IC50）分别为 160nM 和 4.23μM。在本研究中，我们通过口服或腹腔内给药的方式，研究了 DB750 和硝唑尼特对感染实验的 Balb/c 小鼠的作用。在实验 1 中，DB750（2mg/kg/天）和硝唑尼特（150mg/kg/天）的给药于感染前 3 天开始，即在小鼠感染 2×106 速殖子之前。感染后，药物进一步每天口服或腹腔内给药 2 周。DB750 腹腔内注射耐受良好，但硝唑尼特治疗导致所有小鼠在 3 天内死亡。与其他所有组相比，DB750 腹腔内应用可显著降低脑部寄生虫负荷，而 DB750 和硝唑尼特口服应用则效果不佳，且导致明显的体重减轻。在实验 2 中，小鼠感染 2×106 速殖子，感染后 2 周，通过腹腔内注射 DB750（2mg/kg/天）治疗 14 天。在 DB750 治疗组中，12 只小鼠中有 2 只死于感染，而安慰剂组中有 7 只。DB750 治疗还可显著降低脑部寄生虫负荷和活速殖子数量。我们的数据表明，DB750 穿过血脑屏障后仍具有活性，这类化合物可能是控制刚地弓形虫相关疾病的有前途的药物。
