In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection.
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2019
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New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents
problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial
compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low
toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro
effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy
of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model
against L. amazonensis infection. Amphotericin B (AmB) and Ambisome® were used as controls. The animals were
infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome®
, Flau-A or Flau-A/M-treated
animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those
presenting the most significant reductions in the parasite burden, when compared to the others. These animals
developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher
levels of IFN-γ, IL-12, TNF-α, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have
showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M
compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis.
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Chemotherapy, Amphotericin B, Tegumentary leishmaniasis, Toxicity
Citação
MENDONÇA, D. V. C. et al. In vivo antileishmanial efficacy of a naphthoquinone derivate incorporated into a Pluronic® F127-based polymeric micelle system against Leishmania amazonensis infection. Biomedicine & Pharmacotherapy, v. 109, p. 779-787, jan. 2019. Disponível em: <https://www.sciencedirect.com/science/article/pii/S0753332218367878>. Acesso em: 22 fev. 2019.