title: An effective in vitro and in vivo antileishmanial activity and mechanism of action of 8-hydroxyquinoline against Leishmania species causing visceral and tegumentary leishmaniasis.
abstract: The development of new therapeutic strategies to treat leishmaniasis has become a priority. In the present study, the antileishmanial activity of 8-hydroxyquinoline (8-HQN) was investigated against in vitro promastigotes and in vivo intra-macrophage amastigotes of three Leishmania species: Leishmania amazonensis, Leishmania infantum and Leishmania braziliensis. Studies were performed to establish the 50% Leishmania inhibitory concentration (IC50) of 8-HQN, as well as its 50% cytotoxic concentration (CC50) on murine macrophages and in human red blood cells. The inhibition of macrophages infection was also evaluated using parasites that were pre-treated with 8-HQN. The effects of this compound on nitric oxide (NO) production and in the mitochondrial membrane potential were also evaluated. Finally, the therapeutic efficacy of 8-HQN was assessed in a known murine model, L. amazonensis-chronically infected BALB/c mice. Our results showed that 8-HQN was effective against promastigote and amastigote stages of all tested Leishmania species, presenting a selectivity index of 328.0, 62.0 and 47.0 for L. amazonensis, L. infantum and L. braziliensis, respectively. It was effective in treating infected macrophages, as well as in preventing the infection of these cells using pre-treated parasites. In addition, 8-HQN caused an alteration in the mitochondrial membrane potential of the parasites. When administered at 10mg/kg body weight/day by subcutaneous route, this product was effective in reducing the lesion diameter, as well as the parasite load in evaluated tissues and organs of infected animals. The results showed the in vitro and in vivo efficacy of 8-HQN against three different Leishmania species causing tegumentary and/or visceral leishmaniasis, and it could well be used for future therapeutic optimization studies to treat leishmaniasis.
authors.affiliation: Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Costa Duarte
authors.affiliation: Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil.
authors.forename: Letícia Martins
authors.initials: LM
authors.lastname: dos Reis Lage
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100 Minas Gerais, Brazil.
authors.forename: Daniela Pagliara
authors.initials: DP
authors.lastname: Lage
authors.affiliation: Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, São Paulo, 01246-902 São Paulo, Brazil.
authors.forename: Juliana Tonini
authors.initials: JT
authors.lastname: Mesquita
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100 Minas Gerais, Brazil.
authors.forename: Beatriz Cristina Silveira
authors.initials: BC
authors.lastname: Salles
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil.
authors.forename: Stefânia Neiva
authors.initials: SN
authors.lastname: Lavorato
authors.affiliation: Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Menezes-Souza
authors.affiliation: Departamento de Patologia Clínica, COLTEC, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil.
authors.forename: Bruno Mendes
authors.initials: BM
authors.lastname: Roatt
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil; Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil.
authors.forename: Ricardo José
authors.initials: RJ
authors.lastname: Alves
authors.affiliation: Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, 31270-901 Minas Gerais, Brazil.
authors.forename: Carlos Alberto Pereira
authors.initials: CA
authors.lastname: Tavares
authors.affiliation: Centro de Parasitologia e Micologia, Instituto Adolfo Lutz, São Paulo, 01246-902 São Paulo, Brazil.
authors.forename: André Gustavo
authors.initials: AG
authors.lastname: Tempone
authors.affiliation: Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100 Minas Gerais, Brazil. Electronic address: eduardoferrazcoelho@yahoo.com.br.
authors.forename: Eduardo Antonio Ferraz
authors.initials: EA
authors.lastname: Coelho
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D007892:Leishmania braziliensis / Q000187:drug effects; D018314:Leishmania infantum / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy; D007898:Leishmaniasis, Visceral / Q000188:drug therapy; D008264:Macrophages / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D015125:Oxyquinoline / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D059208:Parasite Load; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D015125:Oxyquinoline
keywords: 8-Hydroxyquinoline; Antileishmanial activity; Leishmania; Leishmaniasis; Toxicity; Treatment