Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Egypt.
Exp Parasitol. 2011 Aug;128(4):382-90. doi: 10.1016/j.exppara.2011.05.009. Epub 2011 May 19.
Leishmaniasis is a family of diseases caused by protozoan parasites of the genus Leishmania. Various Leishmania species can cause human infection, producing a spectrum of clinical manifestations. The current treatments are unsatisfactory, and in absence of a vaccine, there is an urgent need for effective drugs to replace/supplement those currently in use. Recent studies have shown that the antineoplastic drug, tamoxifen, had direct leishmanicidal effect on several Leishmania species in vitro. Moreover, in vivo testing was carried out on some of the species and showed promising results. The authors have carried out the present work to complement previous published studies by investigating in vivo activity of tamoxifen in an experimental model of cutaneous leishmaniasis (CL) caused by Leishmania major. Groups of infected mice were given tamoxifen, orally, at a dose of 20 mg/kg/day for 15 days. Efficacy was assessed clinically, parasitologically, histopathologically by light and transmission electron microscope (TEM). Results showed that untreated infected mice suffered from autoamputation of the inoculated foot pad. However, those which received tamoxifen showed marked improvement of the cutaneous lesions and reduction of parasite burden. TEM of the cutaneous lesions from infected mice revealed the fine structure of normal Leishmania amastigotes, whereas those from infected mice treated with tamoxifen showed considerable changes. All male mice that received tamoxifen showed scrotal swelling with evident histopathological changes in the testes that could seriously compromise fertility of male mice. In conclusion, although tamoxifen causes significant side effects to the male reproductive system in the mouse model, it could provide an alternative to current agents. Results of this study demonstrated in vivo activity of tamoxifen against Leishmania major, thus, suggesting that tamoxifen is a suitable lead for the synthesis of more effective and less toxic antileishmanial derivatives.
利什曼病是一类由利什曼原虫属原生动物寄生虫引起的疾病。各种利什曼原虫可引起人类感染，产生一系列临床表现。目前的治疗方法并不令人满意，而且在没有疫苗的情况下，迫切需要有效的药物来替代/补充目前正在使用的药物。最近的研究表明，抗肿瘤药物他莫昔芬对几种利什曼原虫在体外具有直接杀利什曼原虫作用。此外，对一些物种进行了体内测试，结果显示出有希望的结果。作者进行了这项工作，通过研究他莫昔芬在由利什曼原虫引起的皮肤利什曼病（CL）实验模型中的体内活性，对以前发表的研究进行了补充。感染小鼠的组接受他莫昔芬，口服，剂量为 20mg/kg/天，持续 15 天。临床、寄生虫学、组织病理学（光镜和透射电镜）评估疗效。结果显示，未治疗的感染小鼠接种的足底发生自动截肢。然而，接受他莫昔芬治疗的小鼠皮肤病变明显改善，寄生虫负担减少。受感染小鼠皮肤病变的 TEM 显示正常利什曼原虫无鞭毛体的精细结构，而用他莫昔芬治疗的感染小鼠显示出相当大的变化。所有接受他莫昔芬的雄性小鼠均出现阴囊肿胀，睾丸明显的组织病理学变化，可能严重损害雄性小鼠的生育能力。总之，尽管他莫昔芬在小鼠模型中对男性生殖系统造成严重的副作用，但它可以作为当前药物的替代品。本研究结果表明他莫昔芬对利什曼原虫具有体内活性，因此表明他莫昔芬是合成更有效和毒性更小的抗利什曼原虫衍生物的合适先导化合物。
