Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana
Leishmaniasis is a worldwide parasitic disease, caused by monoflagellate parasites of the genus Leishmania. In the search for more effective agents against these parasites, the identification of molecular targets has been attempted to ensure the efficiency of drugs and to avoid collateral damages on...
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doaj-92f46def34ad4a64a7040b9e24c9e20f2020-11-24T22:39:50ZengHindawi LimitedEvidence-Based Complementary and Alternative Medicine1741-427X1741-42882013-01-01201310.1155/2013/163404163404Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicanaPatricia Barrera0Valeria P. Sülsen1Esteban Lozano2Mónica Rivera3María Florencia Beer4Carlos Tonn5Virginia S. Martino6Miguel A. Sosa7Instituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo (UNCuyo), CC 56 (5500) Mendoza, ArgentinaInstituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Cátedra de Farmacognosia, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 2°P, 1113 Buenos Aires, ArgentinaInstituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo (UNCuyo), CC 56 (5500) Mendoza, ArgentinaInstituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo (UNCuyo), CC 56 (5500) Mendoza, ArgentinaInstituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Cátedra de Farmacognosia, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 2°P, 1113 Buenos Aires, ArgentinaInstituto de Investigaciones en Tecnología Química (INTEQUI-CONICET), Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, ArgentinaInstituto de Química y Metabolismo del Fármaco (IQUIMEFA) (UBA-CONICET), Cátedra de Farmacognosia, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 2°P, 1113 Buenos Aires, ArgentinaInstituto de Histología y Embriología “Dr. Mario H. Burgos” (IHEM-CONICET), Facultad de Ciencias Médicas, Universidad Nacional de Cuyo (UNCuyo), CC 56 (5500) Mendoza, ArgentinaLeishmaniasis is a worldwide parasitic disease, caused by monoflagellate parasites of the genus Leishmania. In the search for more effective agents against these parasites, the identification of molecular targets has been attempted to ensure the efficiency of drugs and to avoid collateral damages on the host’s cells. In this work, we have investigated some of the mechanisms of action of a group of natural sesquiterpene lactones that are effective against Leishmania mexicana mexicana promastigotes. We first observed that the antiproliferative effect of mexicanin I (Mxc), dehydroleucodine (DhL), psilostachyin (Psi), and, at lesser extent, psilostachyin C (Psi C) is blocked by 1.5 mM reduced glutathione. The reducing agent was also able to reverse the early effect of the compounds, suggesting that lactones may react with intracellular sulfhydryl groups. Moreover, we have shown that all the sesquiterpene lactones, except Psi C, significantly decreased the endogenous concentration of glutathione within the parasite. Consistent with these findings, the active sesquiterpene lactones increased between 2.7 and 5.4 times the generation of ROS by parasites. These results indicate that the induction of oxidative stress is at least one of the mechanisms of action of DhL, Mxc, and Psi on parasites while Psi C would act by another mechanism.http://dx.doi.org/10.1155/2013/163404 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Patricia Barrera Valeria P. Sülsen Esteban Lozano Mónica Rivera María Florencia Beer Carlos Tonn Virginia S. Martino Miguel A. Sosa |
spellingShingle |
Patricia Barrera Valeria P. Sülsen Esteban Lozano Mónica Rivera María Florencia Beer Carlos Tonn Virginia S. Martino Miguel A. Sosa Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana Evidence-Based Complementary and Alternative Medicine |
author_facet |
Patricia Barrera Valeria P. Sülsen Esteban Lozano Mónica Rivera María Florencia Beer Carlos Tonn Virginia S. Martino Miguel A. Sosa |
author_sort |
Patricia Barrera |
title |
Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana |
title_short |
Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana |
title_full |
Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana |
title_fullStr |
Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana |
title_full_unstemmed |
Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana |
title_sort |
natural sesquiterpene lactones induce oxidative stress in leishmania mexicana |
publisher |
Hindawi Limited |
series |
Evidence-Based Complementary and Alternative Medicine |
issn |
1741-427X 1741-4288 |
publishDate |
2013-01-01 |
description |
Leishmaniasis is a worldwide parasitic disease, caused by monoflagellate parasites of the genus Leishmania. In the search for more effective agents against these parasites, the identification of molecular targets has been attempted to ensure the efficiency of drugs and to avoid collateral damages on the host’s cells. In this work, we have investigated some of the mechanisms of action of a group of natural sesquiterpene lactones that are effective against Leishmania mexicana mexicana promastigotes. We first observed that the antiproliferative effect of mexicanin I (Mxc), dehydroleucodine (DhL), psilostachyin (Psi), and, at lesser extent, psilostachyin C (Psi C) is blocked by 1.5 mM reduced glutathione. The reducing agent was also able to reverse the early effect of the compounds, suggesting that lactones may react with intracellular sulfhydryl groups. Moreover, we have shown that all the sesquiterpene lactones, except Psi C, significantly decreased the endogenous concentration of glutathione within the parasite. Consistent with these findings, the active sesquiterpene lactones increased between 2.7 and 5.4 times the generation of ROS by parasites. These results indicate that the induction of oxidative stress is at least one of the mechanisms of action of DhL, Mxc, and Psi on parasites while Psi C would act by another mechanism. |
url |
http://dx.doi.org/10.1155/2013/163404 |
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