In Vitro and in Vivo Activity of an Organic Tellurium Compound on Leishmania (Leishmania) chagasi

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dc.contributor.authorPimentel, Isabella Aparecida Salerno [UNIFESP]
dc.contributor.authorPaladi, Carolina de Siqueira [UNIFESP]
dc.contributor.authorKatz, Simone [UNIFESP]
dc.contributor.authorJudice, Wagner Alves de Souza [UNIFESP]
dc.contributor.authorCunha, Rodrigo Luiz Oliveira Rodrigues [UNIFESP]
dc.contributor.authorBarbieri, Clara Lucia [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Mogi das Cruzes
dc.contributor.institutionUniversidade Federal do ABC (UFABC)
dc.date.accessioned2016-01-24T14:28:00Z
dc.date.available2016-01-24T14:28:00Z
dc.date.issued2012-11-07
dc.description.abstractTellurium compounds have shown several biological properties and recently the leishmanicidal effect of one organotellurane was demonstrated. These findings led us to test the effect of the organotellurium compound RF07 on Leishmania (Leishmania) chagasi, the agent of visceral leishmaniasis in Latin America. in vitro assays were performed in L. (L.) chagasi-infected bone marrow derived macrophages treated with different concentrations of RF07. in in vivo experiments Golden hamsters were infected with L. (L.) chagasi and injected intraperitoneally with RF07 whereas control animals received either Glucantime or PBS. the effect of RF07 on cathepsin B activity of L. (L.) chagasi amastigotes was assayed spectrofluorometrically using fluorogenic substrates. the main findings were: 1) RF07 showed significant leishmanicidal activity against intracellular parasites at submicromolar concentrations (IC50 of 529.7+/-26.5 nM), and the drug displayed 10-fold less toxicity to macrophages (CC50 of 5,426+/-272.8 nM); 2) kinetics assays showed an increasing leishmanicidal action of RF07 at longer periods of treatment; 3) one month after intraperitoneal injection of RF07 L. (L.) chagasi-infected hamsters showed a reduction of 99.6% of parasite burden when compared to controls that received PBS; 4) RF07 inhibited the cathepsin B activity of L. (L.) chagasi amastigotes. the present results demonstrated that the tellurium compound RF07 is able to destroy L. (L.) chagasi in vitro and in vivo at concentrations that are non toxic to the host. We believe these findings support further study of the potential of RF07 as a possible alternative for the chemotherapy of visceral leishmaniasis.en
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil
dc.description.affiliationUniv Mogi das Cruzes, Ctr Interdisciplinar Invest Bioquim, São Paulo, Brazil
dc.description.affiliationUniv Fed ABC, Ctr Ciencias Nat & Humanas, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipInstituto de Pesquisa, Informacao e Tecnologia da Amazonia (IPITAM)
dc.format.extent7
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0048780
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 7, n. 11, 7 p., 2012.
dc.identifier.doi10.1371/journal.pone.0048780
dc.identifier.fileWOS000311935800130.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35501
dc.identifier.wosWOS:000311935800130
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleIn Vitro and in Vivo Activity of an Organic Tellurium Compound on Leishmania (Leishmania) chagasien
dc.typeinfo:eu-repo/semantics/article
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