Bothrops leucurus venom induces nephrotoxicity in the isolated perfused kidney and cultured renal tubular epithelia

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dc.contributor.authorOliveira de Morais, Isabel Cristina
dc.contributor.authorCosta Torres, Alba Fabiola
dc.contributor.authorSilva Pereira, Gustavo Jose da [UNIFESP]
dc.contributor.authorPereira, Ticiana Praciano
dc.contributor.authorPessoa Bezerra de Menezes, Ramon Roseo de Paula
dc.contributor.authorMello, Clarissa Perdigao
dc.contributor.authorCoelho Jorge, Antonio Rafael
dc.contributor.authorBinda, Alexandre Havt
dc.contributor.authorToyama, Marcos Hikari
dc.contributor.authorAzul Monteiro, Helena Serra
dc.contributor.authorSmaili, Soraya Soubhi [UNIFESP]
dc.contributor.authorCosta Martins, Alice Maria
dc.contributor.institutionUniv Fed Ceara
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionPaulista State Univ UNESP
dc.date.accessioned2016-01-24T14:31:04Z
dc.date.available2016-01-24T14:31:04Z
dc.date.issued2013-01-01
dc.description.abstractBites from snake (Bothrops genus) cause local tissue damage and systemic complications, which include alterations such as hemostatic system and acute renal failure (ARF). Recent studies suggest that ARF pathogenesis in snakebite envenomation is multifactorial and involves hemodynamic disturbances, immunologic reactions and direct nephrotoxicity. the aim of the work was to investigate the effects of the Bothrops leucurus venom (BlV) in the renal perfusion system and in cultured renal tubular cells of the type MDCK (Madin-Darby Canine kidney). BlV (10 mu g/mL) reduced the perfusion pressure at 90 and 120 min. the renal vascular resistance (RVR) decreased at 120 min of perfusion. the effect on urinary flow (UF) and glomerular filtration rate (CFR) started 30 min after BlV infusion, was transient and returned to normal at 120 min of perfusion. It was also observed a decrease on percentual tubular transport of sodium (%TNa+) at 120 min and of chloride (%TCl-) at 60 and 90 min. the treatment with BlV caused decrease in cell viability to the lowest concentration tested with an IC50 of 1.25 mu g/mL. Flow cytometry with annexin V and propidium iodide showed that cell death occurred predominantly by necrosis. However, a cell death process may involve apoptosis in lower concentrations. BlV treatment (1.25 mu g/mL) led to significant depolarization of the mitochondrial membrane potential and, indeed, we found an increase in the expression of cell death genes in the lower concentrations tested. the venom also evoked an increase in the cytosolic Ca2+ in a concentration dependent manner, indicating that Ca2+ may participate in the venom of B. leucurus effect. the characterization of the effects in the isolated kidney and renal tubular cells gives strong evidences that the acute renal failure induced by this venom is a result of the direct nephrotoxicity which may involve the cell death mechanism. Published by Elsevier B.V.en
dc.description.affiliationUniv Fed Ceara, Fac Med, Dept Physiol & Pharmacol, Fortaleza, Ceara, Brazil
dc.description.affiliationUniv Fed Ceara, Dept Clin & Toxicol Anal, Fortaleza, Ceara, Brazil
dc.description.affiliationFed Univ São Paulo UNIFESP EPM, Dept Pharmacol, São Paulo, Brazil
dc.description.affiliationPaulista State Univ UNESP, Sao Vicente Unit, São Paulo, Brazil
dc.description.affiliationUnifespFed Univ São Paulo UNIFESP EPM, Dept Pharmacol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent38-46
dc.identifierhttp://dx.doi.org/10.1016/j.toxicon.2012.10.005
dc.identifier.citationToxicon. Oxford: Pergamon-Elsevier B.V., v. 61, p. 38-46, 2013.
dc.identifier.doi10.1016/j.toxicon.2012.10.005
dc.identifier.issn0041-0101
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/35817
dc.identifier.wosWOS:000314146400006
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofToxicon
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectBothrops leucurusen
dc.subjectNephrotoxicityen
dc.subjectRenal tubular epitheliaen
dc.titleBothrops leucurus venom induces nephrotoxicity in the isolated perfused kidney and cultured renal tubular epitheliaen
dc.typeinfo:eu-repo/semantics/article
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