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色甘酸钠和酮替芬对体外及体内弓形虫进入宿主细胞的抑制作用。

The inhibitory effect of cromolyn sodium and ketotifen on Toxoplasma gondii entrance into host cells in vitro and in vivo.

作者信息

Rezaei Fatemeh, Ebrahimzadeh Mohammad Ali, Daryani Ahmad, Sharif Mehdi, Ahmadpour Ehsan, Sarvi Shahabeddin

机构信息

Toxoplasmosis Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Pharmaceutical Sciences Research Center, School of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

J Parasit Dis. 2016 Sep;40(3):1001-5. doi: 10.1007/s12639-014-0623-3. Epub 2014 Dec 20.

Abstract

Toxoplasma gondii is a protozoan with worldwide distribution and in spite of increasing information about its biology, treatment of toxoplasmosis is restricted to a few drugs and unfortunately using of each of drugs is associated with significant side effects in patients. This study was designed to evaluate the efficacy of cromolyn sodium and ketotifen as alternative drugs for the treatment of toxoplasmosis. In vitro; in case group, concentrations of 1, 5, 10 and 15 µg/ml of ketotifen and cromolyn sodium were added to RPMI medium containing peritoneal macrophages. After 1 h incubation and adding tachyzoites to medium, efficacy rate of these drugs in entrance inhibition of Toxoplasma tachyzoites into macrophages were evaluated after 30 and 60 min. In vivo; case groups received ketotifen and cromolyn sodium with different concentrations at various times. Control groups received none of drugs. We found that in vitro; after 60 min the best efficacy of these drugs in inhibition of cell entrance of Toxoplasma was observed at 15 µg/ml (78.9 ± 1.70 and 91.97 ± 0.37 %, respectively) (P < 0.05). In vivo; after 60 min ketotifen at 2 mg/kg in 3 h before tachyzoite injection (69.83 ± 2.25 %), and cromolyn sodium, at 10 mg/kg in 6 h before tachyzoite injection (80.47 ± 2/49 %) had the best effect on inhibition of Toxoplasma entry into the cells (P < 0.05). Our findings show that ketotifen and cromolyn sodium are suitable drugs for entrance inhibition of tachyzoites into nucleated cells in vitro and in vivo.

摘要

刚地弓形虫是一种分布于全球的原生动物,尽管关于其生物学的信息不断增加,但弓形虫病的治疗仅限于少数几种药物,不幸的是,每种药物的使用都会给患者带来显著的副作用。本研究旨在评估色甘酸钠和酮替芬作为治疗弓形虫病替代药物的疗效。体外实验中,在病例组,将浓度为1、5、10和15微克/毫升的酮替芬和色甘酸钠添加到含有腹腔巨噬细胞的RPMI培养基中。孵育1小时后向培养基中加入速殖子,30分钟和60分钟后评估这些药物对弓形虫速殖子进入巨噬细胞的抑制率。体内实验中,病例组在不同时间接受不同浓度的酮替芬和色甘酸钠。对照组不接受任何药物。我们发现,体外实验中,60分钟后,这些药物在15微克/毫升时对弓形虫细胞进入的抑制效果最佳(分别为78.9±1.70%和91.97±0.37%)(P<0.05)。体内实验中,速殖子注射前3小时给予2毫克/千克酮替芬(69.83±2.25%),速殖子注射前6小时给予10毫克/千克色甘酸钠(80.47±2.49%)对抑制弓形虫进入细胞的效果最佳(P<0.05)。我们的研究结果表明,酮替芬和色甘酸钠是体外和体内抑制速殖子进入有核细胞的合适药物。

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