Velásquez-Torres Maritza, Trujillo-Ferrara José Guadalupe, Godínez-Victoria Marycarmen, Jarillo-Luna Rosa Adriana, Tsutsumi Víctor, Sánchez-Monroy Virginia, Posadas-Mondragón Araceli, Cuevas-Hernández Roberto Issac, Santiago-Cruz José Angel, Pacheco-Yépez Judith
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico.
Laboratorio de Investigación en Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico.
Pharmaceuticals (Basel). 2023 Jun 19;16(6):896. doi: 10.3390/ph16060896.
Amoebiasis is produced by the parasite ; this disease affects millions of people throughout the world who may suffer from amoebic colitis or amoebic liver abscess. Metronidazole is used to treat this protozoan, but it causes important adverse effects that limit its use. Studies have shown that riluzole has demonstrated activity against some parasites. Thus, the present study aimed, for the first time, to demonstrate the in vitro and in silico anti-amoebic activity of riluzole. In vitro, the results of trophozoites treated with IC (319.5 μM) of riluzole for 5 h showed (i) a decrease of 48.1% in amoeba viability, (ii) ultrastructural changes such as a loss of plasma membrane continuity and alterations in the nuclei followed by lysis, (iii) apoptosis-like cell death, (iv) the triggering of the production of reactive oxygen species and nitric oxide, and (v) the downregulation of amoebic antioxidant enzyme gene expression. Interestingly, docking studies have indicated that riluzole presented a higher affinity than metronidazole for the antioxidant enzymes thioredoxin, thioredoxin reductase, rubrerythrin, and peroxiredoxin of , which are considered as possible candidates of molecular targets. Our results suggest that riluzole could be an alternative treatment against . Future studies should be conducted to analyze the in vivo riluzole anti-amoebic effect on the resolution of amebic liver abscess in a susceptible model, as this will contribute to developing new therapeutic agents with anti-amoebic activity.
阿米巴病由该寄生虫引起;这种疾病影响着全世界数百万人,他们可能患有阿米巴结肠炎或阿米巴肝脓肿。甲硝唑用于治疗这种原生动物,但它会引起严重的不良反应,限制了其使用。研究表明,利鲁唑已显示出对某些寄生虫的活性。因此,本研究首次旨在证明利鲁唑的体外和计算机模拟抗阿米巴活性。在体外,用利鲁唑的IC(319.5μM)处理滋养体5小时的结果显示:(i)阿米巴活力降低48.1%;(ii)超微结构变化,如质膜连续性丧失、细胞核改变继而溶解;(iii)凋亡样细胞死亡;(iv)活性氧和一氧化氮产生的触发;(v)阿米巴抗氧化酶基因表达的下调。有趣的是,对接研究表明,利鲁唑对硫氧还蛋白、硫氧还蛋白还原酶、红素氧还蛋白和过氧化物氧还蛋白等抗氧化酶的亲和力高于甲硝唑,这些酶被认为是可能的分子靶点候选物。我们的结果表明,利鲁唑可能是治疗[疾病名称未明确]的一种替代疗法。未来应开展研究,分析利鲁唑在易感模型中对阿米巴肝脓肿消退的体内抗阿米巴作用,因为这将有助于开发具有抗阿米巴活性的新治疗药物。