Contribution of Microscopy for Understanding the Mechanism of Action Against Trypanosomatids

  • Esteban Lozano
  • Renata Spina
  • Patricia Barrera
  • Carlos Tonn
  • Miguel A. SosaEmail author


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.


Natural compounds Terpenes Bioactive molecules Trypanosomatids Trypanosomatid ultrastructure Neglected tropical diseases 


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Authors and Affiliations

  • Esteban Lozano
    • 1
  • Renata Spina
    • 2
  • Patricia Barrera
    • 2
  • Carlos Tonn
    • 3
  • Miguel A. Sosa
    • 2
    Email author
  1. 1.Laboratorio de Inmunología y Desarrollo de Vacunas, Instituto de Medicina y Biología Experimental de Cuyo (IMBECU, CCT-CONICET)MendozaArgentina
  2. 2.Laboratorio de Biología y Fisiología Celular Dr. Francisco Bertini, Instituto de Histología y Embriología (IHEM-CONICET)MendozaArgentina
  3. 3.Instituto de Investigación en Tecnología Química (INTEQUI), Facultad de Química Bioquímica y Farmacia, Universidad Nacional de San LuisSan LuisArgentina

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