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dc.creatorRodrigues, Veridiana M.
dc.creatorSoares, Andreimar Martins
dc.creatorAndrião Escarso, Silvia H.
dc.creatorFranceschi, Aida
dc.creatorRucavado Romero, Alexandra
dc.creatorGutiérrez, José María
dc.creatorGiglio, José Roberto
dc.date.accessioned2017-02-02T15:53:12Z
dc.date.available2017-02-02T15:53:12Z
dc.date.issued2001-06
dc.identifier.citationhttp://www.sciencedirect.com/science/article/pii/S0300908401012822
dc.identifier.issn0300-9084
dc.identifier.urihttps://hdl.handle.net/10669/29482
dc.description.abstractThe pathological alterations induced by neuwiedase, a 22 kDa class P-I metalloproteinase from the venom of the South American pit viper Bothrops neuwiedi, were studied in mice. Neuwiedase was devoid of hemorrhagic activity when tested in the skin up to a dose of 200 μg, and also after intramuscular injection in the gastrocnemius. However, it induced bleeding when applied onto the mouse cremaster muscle in intravital microscopy experiments, and caused pulmonary hemorrhage when injected intravenously at doses higher than 5 μg/g. Median lethal dose (LD50) by the intravenous route was 5 μg/g, whereas LD50 of crude venom was 0.47 μg/g. After intramuscular injection, neuwiedase induced a mild myotoxic effect, evidenced histologically and by the increment in plasma creatine kinase activity, but it was devoid of hemorrhagic and thrombotic effects. In contrast, crude B. neuwiedi venom induced prominent hemorrhage and myonecrosis in gastrocnemius muscle. Both venom and neuwiedase induced an inflammatory reaction in muscle tissue characterized by abundant polymorphonuclear leukocytes. Moreover, a conspicuous edema developed in the foot pad after subcutaneous injection of neuwiedase. Anti-neuwiedase antibodies produced in rabbits were effective in the neutralization of hemorrhagic activity of crude venom, evidencing immunological cross-reactivity between neuwiedase and other hemorrhagic metalloproteinases present in the venom, and suggesting that metalloproteinases devoid of, or having low, hemorrhagic activity could be good immunogens to generate antibodies effective against high molecular mass metalloproteinasas having potent hemorrhagic activity. It is concluded that neuwiedase, despite its lack of hemorrhagic effect when injected in the gastrocnemius muscle, contributes to local tissue damage by inducing edema, inflammatory infiltrate and mild myotoxicity, and by degrading extracellular matrix components. In addition, large doses of neuwiedase may contribute to pulmonary bleedinges_ES
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico//CNPq/Brasiles_ES
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo//FAPESP/Brasiles_ES
dc.description.sponsorshipInternational Foundation for Science/[F/2707]/IFS/Sueciaes_ES
dc.description.sponsorshipUniversidad de Costa Rica/[741-98-202]/UCR/Costa Ricaes_ES
dc.language.isoen_USes_ES
dc.sourceBiochimie; Volumen 83, Número 6. 2001es_ES
dc.subjectMetalloproteinasees_ES
dc.subjectHemorrhagees_ES
dc.subjectMyotoxic Activityes_ES
dc.subjectEdema-inducing Activityes_ES
dc.subjectBothrops Neuwiedies_ES
dc.subjectSnake venomes_ES
dc.titlePathological alterations induced by neuwiedase, a metalloproteinase isolated from Bothrops neuwiedi snake venomes_ES
dc.typeartículo original
dc.identifier.doi10.1016/S0300-9084(01)01282-2
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.identifier.pmid11506891


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