2013-12-062013-12-062013-05-27RODRIGUES, Ana Paula Drummond. Efeito in vitro e in vivo do 5-hidroxi-2-hidroximetil-gama-pirona durante a infecção por Leishmania (Leishmania) amazonensis. 2013. 85 f. Tese (Doutorado) - Universidade Federal do Pará, Instituto de Ciências Biológicas, Belém, 2013. Programa de Pós-Graduação em Neurociências e Biologia Celular.https://repositorio.ufpa.br/handle/2011/4509Leishmaniasis includes a group of infectious diseases with worldwide distribution. Chemotherapy is one of the most effective treatments for this disease; although a number of anti-leishmanial drugs are available, these drugs are in general toxic, expensive and require long-term treatment. Kojic acid, or 5-hydroxy-2-hydroxymethyl-γ-pyrone (HMP), is well known for effectively inhibiting the tyrosinase enzyme in the process of melanin biosynthesis and is extensively used in cosmetics and as a topical treatment for melasm with no cytotoxicity observed in humans; however its potential as anti-leishmanial agent are unknown. The present study was designed to determine the effect of this bioproduct on L. amazonensis, following in vitro and in vivo infections. HMP (50μg/mL) was found to decrease the growth by 62% (IC50 34 μg/mL) and 79% (IC50 27.84 μg/mL) of promastigotes and amastigotes in vitro, respectively. Ultrastructural analysis of both evolutive forms showed that HMP increasing the presence of vesicles bodies into the flagellar pocket, and inducing an intense intracellular vacuolization and swelling of the mitochondrion. In vitro study also demonstrated that HMP is able to reverse ROS inhibitory mechanism promoted by L. amazonensis observed by nitroblue tetrazolium reaction. Histopathologycal analysis of in vivo topical treatment with HMP ointment showed healing process and suppressed ulcer dissemination in animal model. In addition, collagen fibers stained by picrosirus red, were found at the infection site of HMP-treated animals and an absence or low-level cellular infiltrate was observed, as well as a decrease in parasite burden. In view of the in vitro selective action of HMP on leishmania parasites, the activation of host cells and in vivo decrease in parasite burden, observed using HMP ointment, as well as the fact that HMP is widely and safely applied as an antimelasm agent in humans, this compound could be useful for the selective treatment of cutaneous leishmaniasis and may hold great potential as an anti-leishmanial agent.porAcesso AbertoLeishmaniose cutâneaLeishmania amazonensisÁcido kójicoTratamento tópico5-hidroxi-2-hidroximetil-γ-pironaTeseCNPQ::CIENCIAS BIOLOGICAS::PARASITOLOGIA::PROTOZOOLOGIA DE PARASITOS::PROTOZOOLOGIA PARASITARIA HUMANACNPQ::CIENCIAS BIOLOGICAS::MORFOLOGIA::CITOLOGIA E BIOLOGIA CELULAR