| Abstrakt: |
Several ortho -naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi , the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (Tc AKR) reduces o-NQs, such as β -lapachone (β -Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of Tc AKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that Tc AKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β -Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater Tc AKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β -Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether Tc AKR participates in o-NQ activation in intact parasites, β -Lap and 9,10-PQ trypanocidal effect was next evaluated in Tc AKR-overexpressing parasites. Only β -Lap was more effective and induced greater ROS production in Tc AKR-overexpressing epimastigotes than in controls, suggesting that Tc AKR may participate in β -Lap activation. [ABSTRACT FROM AUTHOR] |
