Kulsoom Huma, Baig Abdul Mannan, Siddiqui Ruqaiyyah, Khan Naveed Ahmed
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Pakistan.
Exp Parasitol. 2014 Nov;145 Suppl:S115-20. doi: 10.1016/j.exppara.2014.03.025. Epub 2014 Apr 12.
Granulomatous amoebic encephalitis (GAE) is caused by two protist pathogens, Acanthamoeba spp., and Balamuthia mandrillaris. Although rare, it almost always results in death. In the present study, amoebae were treated with various combinations of clinically-approved drugs, targeting vital cellular receptors and biochemical pathways. The results revealed that among the seven different combinations tested, three proved highly effective against both Acanthamoeba castellanii as well as B. mandrillaris at a concentration of 100μM. These combinations included (i) prochlorperazine plus loperamide; (ii) prochlorperazine plus apomorphine; and (iii) procyclidine plus loperamide. In viability assays, none of the drug-treated amoebae emerged as viable trophozoites, suggesting irreversible amoebicidal effects. Four combinations of drugs tested showed varied potency against A. castellanii and B. mandrillaris at 100μM. The combination of haloperidol and loperamide was highly effective against A. castellanii at 100μM, but potent effects against B. mandrillaris were observed only at 250μM. Digoxin and amlodipine were effective against A. castellanii and B. mandrillaris at 100μM and 250μM, respectively. In contrast, the combination of apomorphine and haloperidol was effective against B. mandrillaris and A. castellanii at 100μM and 250μM, respectively. At 100μM, the combination of procyclidine and amiodarone was effective against neither A. castellanii nor B. mandrillaris. In this case, amoebicidal properties were observed at 750μM for A. castellanii, and 950μM for B. mandrillaris. As these drugs are used clinically against non-communicable diseases, the findings reported here have the potential to be tested in a clinical setting against amoebic encephalitis caused by A. castellanii and B. mandrillaris.
肉芽肿性阿米巴脑炎（GAE）由两种原生生物病原体引起，即棘阿米巴属和曼氏巴贝斯虫。虽然罕见，但几乎总会导致死亡。在本研究中，用针对重要细胞受体和生化途径的多种临床批准药物组合对阿米巴进行处理。结果显示，在所测试的七种不同组合中，三种在100μM浓度下对卡氏棘阿米巴和曼氏巴贝斯虫均显示出高效。这些组合包括：（i）氯丙嗪加洛哌丁胺；（ii）氯丙嗪加阿扑吗啡；（iii）丙环定加洛哌丁胺。在活力测定中，经药物处理的阿米巴中没有一个以活滋养体形式出现，表明具有不可逆的杀阿米巴作用。所测试的四种药物组合在100μM时对卡氏棘阿米巴和曼氏巴贝斯虫显示出不同的效力。氟哌啶醇和洛哌丁胺的组合在100μM时对卡氏棘阿米巴高效，但仅在250μM时对曼氏巴贝斯虫观察到强效作用。地高辛和氨氯地平分别在100μM和250μM时对卡氏棘阿米巴和曼氏巴贝斯虫有效。相比之下，阿扑吗啡和氟哌啶醇的组合分别在100μM和250μM时对曼氏巴贝斯虫和卡氏棘阿米巴有效。在100μM时，丙环定和胺碘酮的组合对卡氏棘阿米巴和曼氏巴贝斯虫均无效。在这种情况下，对卡氏棘阿米巴在750μM时观察到杀阿米巴特性，对曼氏巴贝斯虫在950μM时观察到杀阿米巴特性。由于这些药物临床上用于治疗非传染性疾病，此处报告的研究结果有可能在临床环境中针对由卡氏棘阿米巴和曼氏巴贝斯虫引起的阿米巴脑炎进行测试。
