Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2013, Article ID 163404, 6 pages http://dx.doi.org/10.1155/2013/163404 Research Article Natural Sesquiterpene Lactones Induce Oxidative Stress in Leishmania mexicana Patricia Barrera, 1 Valeria P. Sülsen, 2 Esteban Lozano, 1 Mónica Rivera, 1 María Florencia Beer, 2 Carlos Tonn, 3 Virginia S. Martino, 2 and Miguel A. Sosa 1 1 Instituto de Histolog´ ıa y Embriolog´ ıa “Dr. Mario H. Burgos” (IHEM-CONICET), Facultad de Ciencias M´ edicas, Universidad Nacional de Cuyo (UNCuyo), CC 56 (5500) Mendoza, Argentina 2 Instituto de Qu´ ımica y Metabolismo del F´ armaco (IQUIMEFA) (UBA-CONICET), C´ atedra de Farmacognosia, Facultad de Farmacia y Bioqu´ ımica, Universidad de Buenos Aires, Jun´ ın 956 2 ∘ P, 1113 Buenos Aires, Argentina 3 Instituto de Investigaciones en Tecnolog´ ıa Qu´ ımica (INTEQUI-CONICET), Facultad de Qu´ ımica, Bioqu´ ımica y Farmacia, Universidad Nacional de San Luis, 5700 San Luis, Argentina Correspondence should be addressed to Virginia S. Martino; vmartino@fyb.uba.ar Received 9 April 2013; Accepted 20 May 2013 Academic Editor: William Setzer Copyright © 2013 Patricia Barrera et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Leishmaniasis is a worldwide parasitic disease, caused by monofagellate parasites of the genus Leishmania. In the search for more efective agents against these parasites, the identifcation of molecular targets has been attempted to ensure the efciency 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 efective against Leishmania mexicana mexicana promastigotes. We frst observed that the antiproliferative efect of mexicanin I (Mxc), dehydroleucodine (DhL), psilostachyin (Psi), and, at lesser extent, psilostachyin C (Psi C) is blocked by 1.5 mM reduced glutathione. Te reducing agent was also able to reverse the early efect of the compounds, suggesting that lactones may react with intracellular sulfydryl groups. Moreover, we have shown that all the sesquiterpene lactones, except Psi C, signifcantly decreased the endogenous concentration of glutathione within the parasite. Consistent with these fndings, the active sesquiterpene lactones increased between 2.7 and 5.4 times the generation of ROS by parasites. Tese 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. 1. Introduction Leishmaniasis is a parasitic disease caused by fagellated parasites of the genus Leishmania and transmitted by phle- botomine sandfies. Tese parasites exhibit a heteroxenous life cycle, alternating between intracellular amastigotes in the mammalian cells and fagellate promastigotes in the vector. Leishmaniasis afects about 12 million people worldwide and, according to the World Health Organization (WHO), 2 million of new cases occur annually and 350 million people are considered at risk of contracting leishmaniasis [1]. Te clinical forms of the disease depend on the species of Leishmania involved and include local infections of the skin, subcutaneous tissue, and regional lymphatic nodes (cuta- neous leishmaniasis); metastatic infections of the oronasal mucosa (mucocutaneous leishmaniasis); and disseminated infection involving visceral organs (visceral leishmaniasis) [2]. Leishmaniasis is distributed worldwide with foci of infec- tion in Central and South America, Southern Europe, North and East Africa, the Middle East and India [3]. In Argentina, this parasitosis afects the northern region of the country with an incidence that has increased over the last two decades [4]. Current drugs used to treat leishmaniasis include pen- tavalent antimonials, pentamidine, and amphotericin B, which induce serious toxic efects on patients. Parasite resistance to these drugs has also been described. New formulations, such as liposomal amphotericin B and other drugs (miltefosine, paromomycin), have serious drawbacks such as parenteral route of administration, duration of the