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In vitro leishmanicidal activity of Tityus discrepans scorpion venom
Authors:Adolfo Borges  Sylvia Silva  Huub JM Op den Camp  Elena Velasco  Marco Alvarez  Marcelo JM Alfonzo  Alicia Jorquera  Leonardo De Sousa  Olinda Delgado
Institution:(1) Institute of Experimental Medicine, Central University of Venezuela, Box 50587, Sabana Grande, Caracas, 1051, Venezuela;(2) Sección de Immunoparasitología, Instituto de Medicina Tropical, Universidad Central de Venezuela, Caracas, Venezuela;(3) Department of Microbiology, Faculty of Science, Radboud University Nijmegen, Tooernooiveld 1, Nijmegen, The Netherlands;(4) Escuela José María Vargas, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela;(5) Instituto Anatómico, Universidad Central de Venezuela, Caracas, Venezuela;(6) Centro de Investigaciones en Ciencias de la Salud (CICS), Escuela de Medicina, Universidad de Oriente, Núcleo de Anzoátegui, Puerto La Cruz, Estado Anzoátegui, 6023, Venezuela
Abstract:Leishmania parasites are sensitive to peptides with antimicrobial and ion-channel inhibitory activity. Because scorpion venoms are rich sources of such peptides, the leishmanicidal effect of Tityus discrepans venom was investigated. A negative correlation between cell growth and venom concentration was observed for venom-treated cultures of Leishmania (L.) mexicana mexicana promastigotes; 50% growth inhibition was obtained at 0.4 μg/ml. Light microscopy showed rounded, highly vacuolated L. (L.) m. mexicana cells with impaired flagellar motion after 15 min of incubation at 35 μg/ml. Ultrastructural studies confirmed an intense cytoplasm vacuolation and also enlargement of the flagellar pocket. Survival rates for New World Leishmania promastigotes (75% venom effective concentration, μg/ml) obtained after acute (1 h) venom toxicity tests were: L. (L.) m. mexicana (2.3), Leishmania (V.) braziliensis (11.3), and Leishmania (L.) chagasi (56.2). Heat (90°C) treatment of venom and fraction TdII abolished most of their leishmanicidal effect. Acute toxicity assays performed with Sephadex G-50 fractions indicated that leishmanicidal activity is associated with the venom lowest molecular mass components (2.8–7.4 kDa), as determined by MALDI-TOF mass spectrometry.
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