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不同种类代谢抑制剂诱导的寄生原生动物细胞器超微结构改变。

Ultrastructural alterations in organelles of parasitic protozoa induced by different classes of metabolic inhibitors.

作者信息

Rodrigues Juliany Cola Fernandes, de Souza Wanderley

机构信息

Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, CCS, Bloco G, subsolo, Ilha do Fundão, Rio de Janeiro, RJ, 21.941-902, Brazil.

出版信息

Curr Pharm Des. 2008;14(9):925-38. doi: 10.2174/138161208784041033.

Abstract

Parasitic protozoa such as Leishmania, Trypanosoma, Plasmodium, Toxoplasma gondii, Giardia and Trichomonas are able to cause several diseases affecting millions of people around the world with dramatic consequences to the socio-economic life of the affected countries. Diseases like malaria, leishmaniasis and trypanosomiasis have been classified by the World Health Organization as neglected diseases, because they have been almost completely forgotten by the governments as well as the pharmaceutical companies. The specific chemotherapy currently employed for the treatment of these diseases has serious limitations due to lack of efficacy, toxic side effects, growth of drug-resistance and high costs. Thus, it is urgent to develop new chemotherapeutic agents that are more effective, safe and accessible. In this context, several works have been focused on understanding the effect of different drug-treatments on these parasitic protozoa. Organelles and structures such as mitochondrion, kinetoplast, apicoplast, glycosome, acidocalcisome, hydrogenosome, plasma membrane and the cytoskeleton have been studied using different approaches to identify new targets for the development of new chemotherapeutic agents that are required. Some studies on alterations in the fine structure, as assayed using electron microscopy, have indicated the nature of lesions induced by several drugs, allowing deductions on possible modes of action. Here, we briefly review the available data of the effects of several drugs on the ultrastructure of parasitic protozoa and show how electron microscopy can contribute to elucidate the different mechanisms of these anti-parasitic drugs.

摘要

诸如利什曼原虫、锥虫、疟原虫、弓形虫、贾第虫和滴虫等寄生原生动物能够引发多种疾病,影响着全球数百万人,给受影响国家的社会经济生活带来巨大后果。疟疾、利什曼病和锥虫病等疾病已被世界卫生组织列为被忽视疾病,因为政府和制药公司几乎已将它们完全遗忘。目前用于治疗这些疾病的特定化疗方法存在严重局限性,原因包括疗效不佳、有毒副作用、耐药性增加以及成本高昂。因此,迫切需要开发更有效、安全且易于获取的新型化疗药物。在此背景下,多项研究致力于了解不同药物治疗对这些寄生原生动物的影响。人们已采用不同方法对线粒体、动质体、顶质体、糖体、酸性钙小体、氢化酶体、质膜和细胞骨架等细胞器和结构进行研究,以确定开发所需新型化疗药物的新靶点。一些利用电子显微镜检测细微结构变化的研究表明了几种药物诱导的损伤性质,从而能够推断出可能的作用方式。在此,我们简要回顾几种药物对寄生原生动物超微结构影响的现有数据,并展示电子显微镜如何有助于阐明这些抗寄生虫药物的不同作用机制。

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