Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system.
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2016
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Newtherapeutics are urgently needed to treat visceral leishmaniasis (VL). Due to the fact that drug discovery is a
long and expensive process, the development of delivery systems to carry old and toxic drugs could be considered,
as well as the evaluation of new molecules that have already shown to present biological activity. In this
context, the present study evaluated the in vitro and in vivo antileishmanial activity of an 8-hydroxyquinoline
(8-HQN)-containing polymeric micelle (8-HQN/M) system against Leishmania infantum, the main causative
agent of VL in the Americas. The experimental strategy used was based on the evaluation of the parasite load
by a limiting-dilution technique in the spleen, liver, bone marrow and draining lymph nodes of the infected
and treated animals, as well as by a quantitative PCR (qPCR) technique to also assess the splenic parasite load.
The immune response developed was evaluated by the production of IFN-γ, IL-4, IL-10, IL-12 and GM-CSF cytokines,
as well as by antileishmanial nitrite dosage and antibodies production. Hepatic and renal enzymes were
also investigated to verify cellular injury as a result of treatments toxicity. In the results, 8-HQN/M-treated
mice, when compared to the other groups: saline, free amphotericin B (AmpB, as a drug control), 8-HQN and
B-8-HQN/M (as a micelle control) showed more significant reductions in their parasite burden in all evaluated
organs. These animals also showed an antileishmanial Th1 immunity, which was represented by high levels of
IFN-γ, IL-12, GM-CSF and nitrite, associated with a low production of IL-4 and IL-10 and anti-Leishmania IgG1
isotype antibodies. In addition, any hepatic or renal damage was found in these treated animals. In conclusion,
8-HQN/M was effective in treating L. infantum-infected BALB/c mice, and can be considered alone, or combined
with other drugs, as an alternative treatment for VL.
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DUARTE, M. C. et al. Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system. Parasitology International, v. 65, p. 728-736, 2016. Disponível em: <http://www.sciencedirect.com/science/article/pii/S1383576916302240?via%3Dihub>. Acesso em: 29 ago. 2017.