Little is known of the biochemical composition and functional features of the venoms of poorly known Colombian coral snakes. Here, we provide a preliminary characterization of the venom of two Colombian endemic coral snake species, Micrurus medemi and M. sangilensis, as well as Colombian populations of M. helleri. Electrophoresis and RP-HPLC techniques were used to identify venom components, and assays were conducted to detect enzyme activities, including phospholipase A2, hyaluronidase, and protease activities. The median lethal dose was determined using murine models. Cytotoxic activities in primary cultures from hippocampal neurons and cancer cell lines were evaluated. The venom profiles revealed similarities in electrophoretic separation among proteins under 20 kDa. The differences in chromatographic profiles were significant, mainly between the fractions containing medium-/large-sized and hydrophobic proteins; this was corroborated by a proteomic analysis which showed the expected composition of neurotoxins from the PLA2 (~38%) and 3FTx (~17%) families; however, a considerable quantity of metalloproteinases (~12%) was detected. PLA2 activity and protease activity were higher in M. helleri venom according to qualitative and quantitative assays. M. medemi venom had the highest lethality. All venoms decreased cell viability when tested on tumoral cell cultures, and M. helleri venom had the highest activity in neuronal primary culture. These preliminary studies shed light on the venoms of understudied coral snakes and broaden the range of sources that could be used for subsequent investigations of components with applications to specific diseases. Our findings also have implications for the clinical manifestations of snake envenoming and improvements in its medical management.
Coral Snakes , Snake Bites , Humans , Animals , Mice , Coral Snakes/metabolism , Elapid Venoms/chemistry , Antivenins/metabolism , Colombia , Proteomics , Snake Venoms/metabolism , Phospholipases A2/chemistry , Peptide Hydrolases/metabolism , Elapidae/metabolism
Abstract Introduction: Snakes of the genus Micrurus have fossorial habits, passive temperament and scarce production of powerful venom with neurotoxic characteristics that block the synaptic transmission at the neuromuscular junction. Objective: To present an overview of the neurotoxicity of the Micrurus snake venom, and its functional characterization by ex vivo analysis methods. Materials and methods: A literature review was conducted in MedLine and ScienceDirect using specific terms and their combinations. Search strategy: type of studies: articles on the neurotoxicity of Micrurus snake venom and techniques to determine its neurotoxic activity by in vitro, in vivo and ex vivo models; publication period: articles published until June 2018; publication language: English and Spanish. Results: Out of 88 studies identified in the initial search, 28 were excluded because they did not meet the inclusion criteria (based on reading their titles and abstracts). 8 additional articles (books and reports) were included, since, according to the authors' opinion, they complemented the information reported by the selected studies. The studies included in the review (n=68) were original research papers (n=44), review articles (n = 16), and book chapters, reports, guides and online consultations (n=8). Conclusions: Studies performed using ex vivo muscle and nerve preparations to evaluate the effect of neurotoxins provide a good model for the characterization of the pre-synaptic and post-synaptic effect of the venom produced by snakes of the genus Micrurus.
Resumen Introducción. Las serpientes del género Micrurus son animales de hábitos fosoriales, de temperamento pasivo y escasa producción de un potente veneno con características neurotóxicas que bloquean la transmisión sináptica en la placa neuromuscular. Objetivo. Presentar un panorama general de la neurotoxicidad del veneno de las serpientes Micrurus y su caracterización funcional mediante métodos de análisis ex vivo. Materiales y métodos. Se realizó una revisión de la literatura en MedLine y ScienceDirect usando términos específicos y sus combinaciones. Estrategia de búsqueda: tipo de estudios: artículos sobre la neurotoxicidad del veneno de serpientes Micrurus y técnicas para determinar su actividad neurotóxica mediante modelos in vitro, in vivo y ex vivo; periodo de publicación: sin límite inicial a junio de 2018; idiomas: inglés y español. Resultados. De los 88 estudios identificados en la búsqueda inicial, se excluyeron 28 por no cumplir los criterios de inclusión (basándose en la lectura de títulos y resúmenes); además, se incluyeron 8 documentos adicionales (libros e informes), que, a criterio de los autores, complementaban la información reportada por las referencias seleccionadas. Los estudios incluidos en la revisión (n=68) correspondieron a las siguientes tipologías: investigaciones originales (n=44), artículos de revisión (n=16) y capítulos de libros, informes, guías y consultas en internet (n=8). Conclusiones. Los estudios que describen el uso de preparaciones ex vivo de músculo y nervio para evaluar el efecto de neurotoxinas ofrecen un buen modelo para la caracterización del efecto presináptico y postsináptico del veneno producido por las serpientes Micrurus.
Humans , Elapidae , Coral Snakes , Neuromuscular Junction , Phospholipases A2
