info:eu-repo/semantics/publishedVersion
Contribution of microscopy for understanding the mechanism of action against trypanosomatids
Fecha
2018Registro en:
Lozano, Esteban Sebastián; Spina Zapata, Renata María; Barrera, Patricia Andrea; Tonn, Carlos Eugenio; Sosa Escudero, Miguel Angel; Contribution of microscopy for understanding the mechanism of action against trypanosomatids; Springer International Publishing; 2018; 241-273
978-3-319-78274-4
CONICET Digital
CONICET
Autor
Lozano, Esteban Sebastián
Spina Zapata, Renata María
Barrera, Patricia Andrea
Tonn, Carlos Eugenio
Sosa Escudero, Miguel Angel
Resumen
Transmission electron microscopy (TEM) has proved to be a useful tool to study the ultrastructural alterations and the target organelles of new antitrypanosomatid drugs. Thus, it has been observed that sesquiterpene lactones induce diverse ultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmic vacuolization, appearance of multilamellar structures, condensation of nuclear DNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulation could be related to apoptotic events. Some of the sesquiterpene lactones (e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrial swelling accompanied by a visible kinetoplast deformation as well as the appearance of multivesicular bodies. This mitochondrial swelling could be related to the generation of oxidative stress and associated to alterations in the ergosterol metabolism. The appearance of multilamellar structures and multiple kinetoplasts and flagella induced by the sesquiterpene lactone psilostachyin C indicates that this compound would act at the parasite cell cycle level, in an intermediate stage between kinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexane has proved to induce the external membrane budding on T. cruzi together with an apparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEM studies allow elucidating the possible mechanisms and the subsequent identification of molecular targets for the action of natural compounds on trypanosomatids.