RESUMEN
The search for new therapeutic strategies for leishmaniasis treatment is essential due to the side effects of available drugs and the increasing incidence of resistance to them. Marine sponges use chemical compounds as a defense mechanism, and several of them present interesting pharmacological properties. The aim of this study was to evaluate the in vitro activity of the aqueous extract of the marine sponge Dercitus (Stoeba) latex against Leishmania amazonensis. MIC and toxicity against mammal cells were evaluated through broth microdilution assays. Transmission electron microscopy analysis was performed to assess possible effects on L. amazonensis ultrastructure. Arginase and proteolytic activities were measured by spectrometric methodologies. The extract of Dercitus (Stoeba) latex displayed antileishmanial activity and moderate toxicity against peritonial macrophages. Ultrastructural changes were observed after the growth of L. amazonensis promastigotes in the presence of the extract at 150 µg.ml-1 (IC50), mainly on acidocalcysomes. The extract was able to inhibit the activity of arginase and serine proteases. This study shows that Dercitus (Stoeba) latex aqueous extract may be a novel potential source of protozoa protease inhibitors and drugs that are less toxic to be used in the treatment of L. amazonensis infections.
Asunto(s)
Antiprotozoarios , Leishmania mexicana , Poríferos , Animales , Látex/farmacología , Arginasa/farmacología , Brasil , Leishmania mexicana/ultraestructura , Antiprotozoarios/farmacología , Inhibidores de Proteasas/farmacología , Serina Proteasas/farmacología , MamíferosRESUMEN
Candida albicans is the most important fungal pathogen that causes infections in humans. Biofilms are hard-to-treat structures due to their high antifungal resistance. Saliva is a fluid that contains antimicrobial substances acting as the first-line of defense against pathogens, and its immune components may be potential tools for the discovery of new treatments against candidiasis. To evaluate the activity of histatin 5 and human lactoferrin against biofilm formation. A fluconazole-resistant Candida albicans clinical isolate was used as the model microorganism. Morphogenesis was evaluated by differential counting. Biofilm quantification was performed by XTT reduction assay. Thickness and topography of biofilms were assessed through confocal laser scanning microscopy (CLSM). Histatin 5 inhibited yeast-to-hyphae transition in a dose-dependent manner, while the effect of human lactoferrin on this process was inversely proportional to its concentration. Both compounds were able to significantly inhibit biofilm metabolic activity. Histatin 5 reduced biofilm thickness. Histatin 5 and human lactoferrin exhibited in vitro cytotoxicity against a fluconazole-resistant Candida albicans biofilm, which points to the potential application of these compounds in the treatment of biofilms formed by this fungus, especially in resistant infections.