Miguel Danilo C, Zauli-Nascimento Rogéria C, Yokoyama-Yasunaka Jenicer K U, Katz Simone, Barbiéri Clara L, Uliana Silvia R B
Department of Parasitology, Institute of Biomedical Sciences, Universidade de São Paulo, São Paulo, Brazil.
J Antimicrob Chemother. 2009 Feb;63(2):365-8. doi: 10.1093/jac/dkn509. Epub 2008 Dec 17.
The aim of this study was to evaluate the efficacy of tamoxifen in vivo in experimental models of cutaneous (CL) and visceral leishmaniasis (VL) caused by Leishmania braziliensis and Leishmania chagasi, respectively.
Drug activity was assessed against intracellular amastigotes by treating infected macrophage cultures and evaluating the number of infected cells. In vivo efficacy of tamoxifen was tested in L. braziliensis-infected BALB/c mice and in L. chagasi-infected hamsters. Treatment with 20 mg/kg/day tamoxifen was administered for 15 days by the intraperitoneal route. Efficacy was evaluated through measurements of lesion size, parasite burden at the lesion site or liver and spleen and survival rate.
Tamoxifen killed L. braziliensis and L. chagasi intracellular amastigotes with 50% inhibitory concentrations (IC(50)) of 1.9 +/- 0.2 and 2.4 +/- 0.3 microM, respectively. Treatment of L. braziliensis-infected mice with tamoxifen resulted in significant reductions in lesion size and 99% decrease in parasite burden, compared with mock-treated controls. L. chagasi-infected hamsters treated with tamoxifen showed significant reductions in liver parasite load expressed as Leishman-Donovan units and 95% to 98% reduction in spleen parasite burden. All animals treated with tamoxifen survived while 100% of the mock-treated animals had died by 11 weeks after the interruption of treatment.
Tamoxifen is effective in the treatment of CL and VL in rodent models.
本研究旨在分别评估他莫昔芬在由巴西利什曼原虫和恰加斯利什曼原虫引起的皮肤利什曼病（CL）和内脏利什曼病（VL）实验模型中的体内疗效。
通过处理感染的巨噬细胞培养物并评估感染细胞数量来评估药物对细胞内无鞭毛体的活性。在感染巴西利什曼原虫的BALB/c小鼠和感染恰加斯利什曼原虫的仓鼠中测试他莫昔芬的体内疗效。通过腹腔注射途径以20mg/kg/天的剂量给予他莫昔芬治疗15天。通过测量病变大小、病变部位或肝脏和脾脏的寄生虫负荷以及存活率来评估疗效。
他莫昔芬杀死巴西利什曼原虫和恰加斯利什曼原虫细胞内无鞭毛体的50%抑制浓度（IC50）分别为1.9±0.2和2.4±0.3 microM。与 mock 处理的对照组相比，用他莫昔芬治疗感染巴西利什曼原虫的小鼠导致病变大小显著减小，寄生虫负荷降低99%。用他莫昔芬治疗感染恰加斯利什曼原虫的仓鼠显示，以利什曼-多诺万单位表示的肝脏寄生虫负荷显著降低，脾脏寄生虫负荷降低95%至98%。所有接受他莫昔芬治疗的动物均存活，而100%的mock处理动物在治疗中断后11周内死亡。
他莫昔芬在啮齿动物模型中对CL和VL的治疗有效。
