IMBECU   20882
INSTITUTO DE MEDICINA Y BIOLOGIA EXPERIMENTAL DE CUYO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
THE EFFECT OF 5-EPI-ICETEXONE ON LEISHMANIA AMAZONENSIS. IN VITRO AND IN VIVO APPROACH.
Autor/es:
CIFUENTE, DIEGO; SOSA MIGUEL; LOZANO ESTEBAN; CARGNELUTTI DIEGO; GERMANO MARIA JOSE
Lugar:
Santiago de Chile
Reunión:
Congreso; XXIV CONGRESO LATINOAMERICANO DE PARASITOLOGÍA (FLAP XXIV); 2017
Institución organizadora:
Sociedad Chilena de Parasitología (SOCHIPA)
Resumen:
Leishmaniasis is a parasitic disease caused by flagellated parasites of the genus Leishmania and transmitted by phlebotomine sandflies. These parasites exhibit a heteroxenous life cycle, alternating between intracellular amastigotes in the mammalian cells and flagellate promastigotes in the vector. Leishmaniasis is distributed worldwide and affects about 12 million people worldwide, 2 million of new cases occur annually and 350 million people are at risk of contracting leishmaniasis. The clinical forms of the disease depend on the species of Leishmania involved and include cutaneous, mucocutaneous and visceral leishmaniasis. In Argentina, this parasitosis affects the northern region of the country with an incidence that has increased over the last two decades. Current drugs used to treat leishmaniasis include pentavalent antimonials, pentamidine, and amphotericin B, which induce serious toxic effects on patients. Parasite resistance to these drugs has also been described. Therefore, there is an urgent need for novel candidates to treat this parasitic disease. Thus, one strategy in the search for new compounds is the screening of molecules purified from plant sources. Terpenoid derivatives appear as good candidates, because they are abundant in the plant kingdom and because some of them have shown a significant activity against trypanosomatids. A few years ago, we found that a diterpene (isolated from Salvia gilliessi), 5-epi-icetexone (ICTX), is effective against T. cruzi and Leishmania spp. In this sense, the aim of the present work was to evaluate the possible effect in vitro and in vivo of ICTX on Leishmania amazonensis. ICTX exhibited an antiproliferative effect on promastigotes of L amazonensis, even at very low concentrations. Also, the drug affects the mitochondrial activity of the parasites, as evaluated with MTT. By using the probe 2',7'-Diclocrofluorescein diacetate we measured ROS in parasites and observed that ICTX induces increase of ROS production, which was proportional to the drug concentration. On the other hand, we study the effect of ICTX in an in vivo model of cutaneous leishmaniasis. For this, BALB/c mice were infected in the right footpad with 105 promastigotes of L amazonensis and intraperitoneal treated with a dose of 1 mg/kg/day of ICTX. We did not observe changes in the footpad swelling, parasite load and IgG levels. This lead us to think the possibility of a local treatment that could be more effective to treat cutaneous leishmaniasis.