{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T19:13:07Z","timestamp":1772305987356,"version":"3.50.1"},"reference-count":40,"publisher":"Cambridge University Press (CUP)","issue":"9","license":[{"start":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T00:00:00Z","timestamp":1517788800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Several <jats:italic>ortho<\/jats:italic>-naphthoquinones (o-NQs) have trypanocidal activity against <jats:italic>Trypanosoma cruzi<\/jats:italic>, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (<jats:italic>Tc<\/jats:italic>AKR) reduces o-NQs, such as <jats:italic>\u03b2<\/jats:italic>-lapachone (<jats:italic>\u03b2<\/jats:italic>-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of <jats:italic>Tc<\/jats:italic>AKR activity and expression in two <jats:italic>T. cruzi<\/jats:italic> strains, CL Brener and Nicaragua, showed that <jats:italic>Tc<\/jats:italic>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 <jats:italic>\u03b2<\/jats:italic>-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 <jats:italic>Tc<\/jats:italic>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 <jats:italic>\u03b2<\/jats:italic>-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and <jats:italic>T. cruzi<\/jats:italic> strain analysed. To study whether <jats:italic>Tc<\/jats:italic>AKR participates in o-NQ activation in intact parasites, <jats:italic>\u03b2<\/jats:italic>-Lap and 9,10-PQ trypanocidal effect was next evaluated in <jats:italic>Tc<\/jats:italic>AKR-overexpressing parasites. Only <jats:italic>\u03b2<\/jats:italic>-Lap was more effective and induced greater ROS production in <jats:italic>Tc<\/jats:italic>AKR-overexpressing epimastigotes than in controls, suggesting that <jats:italic>Tc<\/jats:italic>AKR may participate in <jats:italic>\u03b2<\/jats:italic>-Lap activation.<\/jats:p>","DOI":"10.1017\/s0031182018000045","type":"journal-article","created":{"date-parts":[[2018,2,5]],"date-time":"2018-02-05T11:26:15Z","timestamp":1517829975000},"page":"1251-1259","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":8,"title":["<i>Trypanosoma cruzi<\/i>: death phenotypes induced by <i>ortho<\/i>-naphthoquinone substrates of the aldo-keto reductase (<i>Tc<\/i>AKR). Role of this enzyme in the mechanism of action of <i>\u03b2<\/i>-lapachone"],"prefix":"10.1017","volume":"145","author":[{"given":"Patricia Andrea","family":"Garavaglia","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Fernanda","family":"Rubio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Laverri\u00e8re","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura M\u00f3nica","family":"Tasso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura Edith","family":"Fichera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joaqu\u00edn J B","family":"Cannata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela 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