Avaliação do clioquinol para o tratamento das leishmanioses tegumentar e visceral

Abstract

Leishmaniasis can cause different clinical manifestations in the mammalian hosts, which depend mainly on the infecting species and the immune status of the infected hosts. New therapies against disease are desirable, since the current drugs present problems, such as toxicity, high cost and/or parasitic resistance. In a recent study by our research group, a new quinoline-derivative, namely clioquinol (ICHQ, 5-chloro-7-iodo-8-quinolinol), was evaluated for its in vitro antileishmanial action against Leishmania infantum and L. amazonensis species. As result, ICHQ was highly effective against the two parasite species, as well as in the treatment of infected macrophages, causing alterations in the mitochondrial membrane potential, cellular integrity and increase in the production of reactive oxygen species by the parasites. ICHQ was incorporated into a polymeric micelle system based on Poloxamer P407 (ICHQ/M), and the in vivo antileishmanial activity was evaluated against L. amazonensis infection in BALB/c mice. Amphotericin B (AmpB) and its liposomal formulation (Ambisome®) were used as controls. Parasitological and immunological analyses performed 30 days after treatment showed that ICHQ/M-treated and L. amazonensis-infected mice presented a significant reduction of the parasite load, as well as the development of a Th1 immune response, which was characterized by high levels of IFN-γ, IL-12 and GM-CSF, as well as low production of IL-4 and IL-10. In conclusion, ICHQ and its micellar system can be considered as an alternative for the future treatment against leishmaniasis.