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dc.creatorRucavado Romero, Alexandra
dc.creatorEscalante Muñoz, Teresa
dc.creatorGutiérrez, José María
dc.date.accessioned2017-02-07T20:15:17Z
dc.date.available2017-02-07T20:15:17Z
dc.date.issued2014-03-15
dc.identifier.citationhttp://www.sciencedirect.com/science/article/pii/S0041010104000480es_ES
dc.identifier.issn0041-0101
dc.identifier.urihttp://hdl.handle.net/10669/29512
dc.description.abstractThe peptidomimetic hydroxamate metalloproteinase inhibitor batimastat (BB-94) was assessed for its ability to neutralize the systemic effects (lethality, hemorrhage and coagulopathy) induced by the venom of Bothrops asper, the most important snake from a medical standpoint in Central America. Batimastat inhibited lethality when a venom challenge dose of two LD50s was used by intraperitoneal and intravenous routes, with ED50s of 250 and 22 μM, respectively. With a challenge dose of three LD50s, lethality was not abrogated, but a conspicuous and dose-dependent delay in the time of death was observed in mice injected with mixtures of venom plus batimastat. Upon incubation with 500 μM batimastat, venom LD50 increased 2.86-fold (intraperitoneal route) and 2.37-fold (intravenous route), when compared with LD50 of venom alone. Batimastat also inhibited the hemorrhagic effect induced by venom in the lungs after intravenous injection. Moreover, batimastat exerted a significant inhibition of in vitro coagulant and in vivo defibrinogenating effects of venom, evidencing that metalloproteinases play a key role in the coagulopathy characteristic of B. asper envenomation. The remaining uninhibited coagulant effect is due to serine proteinases, i.e. thrombin-like enzymes, since this effect was completely abrogated by the combination of batimastat and PMSF. Our results stress the view that metalloproteinases play a relevant role in the systemic pathophysiology of B. asper envenomation and that metalloproteinase inhibitors may become a therapeutic alternative in this pathology.es_ES
dc.description.sponsorshipUniversidad de Costa Rica/[741-A1-504]/UCR/Costa Ricaes_ES
dc.description.sponsorshipUniversidad de Costa Rica/[741-A2-036]/UCR/Costa Ricaes_ES
dc.description.sponsorshipInternational Foundation for Science/[F-2707-3]/IFS/Sueciaes_ES
dc.description.sponsorshipUnited Nations Educational, Scientific and Cultural Organization/[883.701-3]/UNESCO/es_ES
dc.language.isoen_USes_ES
dc.sourceToxicon; Volumen 43, Número 4. 2004es_ES
dc.subjectMetalloproteinasees_ES
dc.subjectBatimastates_ES
dc.subjectPeptidomimetic hydroxamateses_ES
dc.subjectHemorrhagees_ES
dc.subjectSnake venomes_ES
dc.titleEffect of the metalloproteinase inhibitor batimastat in the systemic toxicity induced by Bothrops asper snake venom: understanding the role of metalloproteinases in envenomationes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.typeArtículo científicoes_ES
dc.identifier.doi10.1016/j.toxicon.2004.01.016
dc.description.procedenceUCR::Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.identifier.codproyecto741-A2-036
dc.identifier.codproyecto741-A1-504
dc.identifier.pmid15051405


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