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

Curr Pharm Des

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.

Published: June 2008

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.

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http://dx.doi.org/10.2174/138161208784041033DOI Listing

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