Contribution of Microscopy for Understanding the Mechanism of Action Against Trypanosomatids

LOZANO E; SPINA R; BARRERA P; CARLOS TONN; SOSA MA

Sesquiterpene lactones; Advances in their Chemistry and Biological Aspects

Springer International Publishing AG, part of Springer Nature

Año: 2018; p. 241 - 271

Transmission electron microscopy (TEM) has proved to be a useful toolto study the ultrastructural alterations and the target organelles of new antitrypanosomatiddrugs. Thus, it has been observed that sesquiterpene lactones induce diverseultrastructural alterations in both T. cruzi and Leishmania spp., such as cytoplasmicvacuolization, appearance of multilamellar structures, condensation of nuclearDNA, and, in some cases, an important accumulation of lipid vacuoles. This accumulationcould be related to apoptotic events. Some of the sesquiterpene lactones(e.g., psilostachyin) have also been demonstrated to cause an intense mitochondrialswelling accompanied by a visible kinetoplast deformation as well as the appearanceof multivesicular bodies. This mitochondrial swelling could be related to thegeneration of oxidative stress and associated to alterations in the ergosterol metabolism.The appearance of multilamellar structures and multiple kinetoplasts and flagellainduced by the sesquiterpene lactone psilostachyin C indicates that thiscompound would act at the parasite cell cycle level, in an intermediate stage betweenkinetoplast segregation and nuclear division. In turn, the diterpene lactone icetexanehas proved to induce the external membrane budding on T. cruzi together with anapparent disorganization of the pericellar cytoskeleton. Thus, ultrastructural TEMstudies allow elucidating the possible mechanisms and the subsequent identificationof molecular targets for the action of natural compounds on trypanosomatids.