Montazeri Mahbobeh, Rezaei Kian, Ebrahimzadeh Mohammad Ali, Sharif Mehdi, Sarvi Shahabeddin, Ahmadpour Ehsan, Rahimi Mohammad Taghi, Pagheh Abdol Satar, Mehrzadi Saeed, Daryani Ahmad
Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Trop Med Health. 2017 Nov 21;45:39. doi: 10.1186/s41182-017-0079-0. eCollection 2017.
Standard treatment of toxoplasmosis is accompanied by severe side effects and low tolerability; accordingly, alternative medicines are critically needed. Ketotifen (KET) as a cell membrane stabilizer could be an appropriate inhibitor of () parasite entrance into the host cells. Therefore, the focus of current study is characterization of the anti- activity of KET in the acute phase of toxoplasmosis in murine model as pre-treatment and post-treatment (before and after infection with RH strain). KET was used intraperitoneally both individually (2 and 3 mg/kg/day) and in combination with pyrimethamine (PYR) (50 mg/kg/day). One week after the post infection, DNA was extracted from brain biopsies samples. Parasite load was calculated using Quantitative-PCR (Q-PCR) in a triplicate reaction for each DNA with the target for at RE (a 529 bp repeat element) gene.
A significant difference between KET and control groups was observed ( < 0.001) in the pre-treatment and post-treatment groups. Both KET and the combination of KET and PYR showed a reduction in the parasite load in brain through the acute phase of the infection. 2 mg/kg/day dose of KET resulted in higher anti- activity (15,698 parasites/ml) compared to 3 mg/kg/day dose of KET (72,898 parasites/ml) in brain in the pre-treatment group. In addition, KET combined with PYR significantly decreased the parasite load in the post-treatment group.
Our results indicated that KET has both prophylactic and therapeutic effects on acute phases of the disease.
弓形虫病的标准治疗伴有严重的副作用和低耐受性；因此，迫切需要替代药物。酮替芬（KET）作为一种细胞膜稳定剂，可能是（）寄生虫进入宿主细胞的合适抑制剂。因此，本研究的重点是在小鼠模型中，对酮替芬在弓形虫病急性期作为预处理和后处理（感染RH株之前和之后）的抗（）活性进行表征。酮替芬单独（2和3毫克/千克/天）以及与乙胺嘧啶（PYR）（50毫克/千克/天）联合腹腔注射使用。感染后一周，从脑活检样本中提取DNA。使用定量聚合酶链反应（Q-PCR）对每个DNA进行一式三份反应，以RE（一个529碱基对重复元件）基因为靶点，计算寄生虫载量。
在预处理组和后处理组中，观察到酮替芬组与对照组之间存在显著差异（<0.001）。酮替芬以及酮替芬与乙胺嘧啶的组合在感染急性期均显示脑内寄生虫载量降低。在预处理组中，2毫克/千克/天剂量的酮替芬在脑内的抗（）活性（15,698个寄生虫/毫升）高于3毫克/千克/天剂量的酮替芬（72,898个寄生虫/毫升）。此外，在治疗后组中，酮替芬与乙胺嘧啶联合使用显著降低了寄生虫载量。
我们的结果表明，酮替芬对该疾病的急性期具有预防和治疗作用。
