Contributions of Ultrastructural Studies to the Cell Biology of Trypanosmatids: Targets for Anti-Parasitic Drugs

Abstract

Protozoan parasites cause disease in humans worldwide, and many fall into the genera Trypanosoma and Leishmania; these parasites are responsible for African trypanosomiasis, Chagas disease and the different forms of Leishmaniasis. Strategies for the development of new drugs against these protozoans have been based on their cell biology and biochemistry complemented by the use of electron microscopy. Trypanosoma and Leishmania have special organelles that are involved in metabolic pathways, which are very distinct from those in mammalian cells; these organelles are potential drug targets. Scanning and transmission electron microscopy can identify not only the target organelles but also alterations to the cell surface and ultrastructural changes that characterize distinct forms of programmed cell death.

In vitro biological action of aqueous extract from roots of Physalis angulata against Leishmania (Leishmania) amazonensis

“…Electron microscopy techniques can be a useful tool in drug studies for the identification of cell surfaces and ultrastructural alterations, as well as specific organelle targets in the parasites. Indeed, identification of morphological changes can help elucidate the mechanisms of drug action [23, 24]. Treatment of promastigotes with 50 or 100 μg/mL AEPa caused a reduction and rounding of the body cellular volume, as well as flagellum duplication, as shown by LM and SEM.…”

“…In a review published by Adade and Souto-Padrón. [24], the authors suggested that these alterations may be caused by the interference of drugs and plant extracts in the process of cell division. Since the division process of L. amazonensis promastigotes treated with AEPa initiated at the posterior instead of the normal anterior position [27, 28], it is possible that the extract interfered with the division process of these cells.…”

“…Studies with Cymbopogon citratus oil against promastigotes of L. chagasi showed multi-septation, and shortening of the cell body and flagellum [29]. This alteration could be caused by cytoskeleton disassembly [24]. In addition, TEM analysis showed the presence of multiple vesicles within the flagellar pocket of AEPa treated-promastigotes.…”

“…Several authors, using plant products, demonstrated similar kinetoplast alterations [18, 34]. The kinetoplast is a unique organelle present only in trypanosomatid protozoa and is, thus, a potential drug target due to its unique structure and function, which is matched in its mammalian host [24, 30, 35]. …”

Ultrastructural Analysis ofLeishmania infantum chagasiPromastigotes Forms TreatedIn Vitrowith Usnic Acid

“…Adade and Souto-Padrón [39] studying the ultrastructures of the genera Trypanosoma and Leishmania regarding the antiparasitic drugs observed that the ultrastructural effects are similar among the various drugs used as well as between herbal medicines, including usnic acid.…”