Department of Medical Parasitology, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Int J Parasitol. 2012 May 1;42(5):443-52. doi: 10.1016/j.ijpara.2012.02.015.
Giardia lamblia, the causative agent of giardiasis, is an intestinal infection with worldwide distribution and high rates of prevalence. Increased resistance of the parasite and the side effects of the reference drugs employed in the treatment of giardiasis make it necessary to seek new therapeutic agents. Therefore,the aim of this study was to examine the activity of hexadecylphosphocholine (miltefosine), a membrane active alkylphospholipid, that is licensed as an antileishmanial agent against giardiasis. The efficacy of miltefosine was evaluated both in vitro and in vivo in Swiss albino mice. Results of the in vitro testing revealed susceptibility of G. lamblia trophozoites to miltefosine with the following effective concentrations:EC50s of between 20 and 40 lM, and EC90s of between 20 and 80 lM. Immediate total lysis of the organisms was achieved by 100 lM. In vivo testing showed that oral administration of miltefosine,in a daily dose regimen course of 20 mg/kg for three successive days, to infected mice resulted in total elimination of the parasite from the intestine and amelioration of intestinal pathology. Scanning and transmission electron microscopy studies revealed that miltefosine induced severe morphological alterations to G. lamblia trophozoites, mainly at the level of cell membrane and adhesive disc. In conclusion,we believe that this is the first study highlighting G. lamblia as a possible new target for miltefosine.
蓝氏贾第鞭毛虫，贾第虫病的病原体，是一种具有全球分布和高流行率的肠道感染。寄生虫的耐药性增加和用于治疗贾第虫病的参考药物的副作用使得寻找新的治疗药物成为必要。因此，本研究的目的是研究十六烷基磷酸胆碱（米替福新）的活性，这是一种膜活性烷基磷脂，被许可作为抗利什曼原虫药物用于治疗贾第虫病。米替福新的疗效在瑞士白化病小鼠体内和体外进行了评估。体外试验结果表明，蓝氏贾第鞭毛虫滋养体对米替福新敏感，有效浓度为 20-40 lM，90%有效浓度为 20-80 lM。100 lM 可立即完全溶解。体内试验表明，连续 3 天每天口服 20mg/kg 米替福新可使感染小鼠肠道内寄生虫完全消除，并改善肠道病理学。扫描和透射电子显微镜研究显示，米替福新诱导蓝氏贾第鞭毛虫滋养体严重的形态改变，主要在细胞膜和黏附盘水平。总之，我们认为这是首次强调蓝氏贾第鞭毛虫可能成为米替福新的新靶点。
