ABSTRACT
BACKGROUND Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs. OBJECTIVES We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis. METHODS Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays. FINDINGS Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism. MAIN CONCLUSIONS γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.
ABSTRACT
BACKGROUND Leishmania parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase. OBJECTIVE The present study aimed to better understand the biological response of Leishmania (Leishmania) amazonensis promastigotes at the cellular level after ketoconazole treatment. METHODS Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment. FINDINGS The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8 strain). MAIN CONCLUSIONS Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in in vitro models.
ABSTRACT
Ophidian accidents constitute a serious problem of public health in the tropical countries. In Central and South America, most of the accidents are caused by Bothrops (90.5%), followed by the Crotalus (7.7%), Lachesis (1.4%) and Micrurus (0.4%) genus. The aim of this work was to evaluate clinical-epidemiological aspects of ophidian accidents reported and treated at the Clinical Hospital at Federal University of Uberlândia, in the central region of Brazil. In this study, 641 medical records from January 1999 to December 2013 were analyzed. The results showed that the accidents were more common in the afternoon, from October to April. The major bite occurrence frequency was attributed to the Bothrops (54.76%), followed by Crotalus (30.58%) and Micrurus (1.40%) snakes. Most of the victims were males (80.34%). The main anatomical regions bitten were the lower and upper limbs, 65.67% and 30.58%, respectively. Approximately 80% of the victims were treated in the first 6 hours after the accident.
Os acidentes ofídicos constituem um sério problema de saúde pública em países tropicais. Nas Américas Central e do Sul, a maioria dos acidentes são causados pelo gênero Bothrops (90,5%), seguido por Crotalus (7,7%), Lachesis (1,4%) e Micrurus (0,4%). O objetivo deste trabalho foi avaliar os aspectos clínico-epidemiológicos dos acidentes ofídicos registrados e tratados no Hospital de Clínicas da Universidade Federal de Uberlândia, na região central do Brasil. Neste estudo, foram analisados 641 prontuários médicos de janeiro de 1999 a dezembro de 2013. Os resultados mostraram que os acidentes ofídicos foram mais comuns durante o período da tarde, de outubro a abril. A maior frequência de ocorrência das picadas foi atribuída às serpentes do gênero Bothrops (54,76%), seguido por Crotalus (30,58%) e Micrurus (1,40%). A maioria das vítimas foi do sexo masculino (80.34%). As principais regiões anatômicas acometidas foram os membros inferiores e superiores, 65,67% e 30,58%, respectivamente. Aproximadamente 80% das vítimas foram tratadas nas primeiras 6 horas após o acidente.