Pharmacological characterization of crotamine effects on mice hind limb paralysis employing both ex vivo and in vivo assays: insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal muscles

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dc.contributorLEDS - Laboratório de Dor e Sinalizaçãopt_BR
dc.contributor.authorLima, Sunamita de Carvalhopt_BR
dc.contributor.authorPorta, Lucas de Carvalhopt_BR
dc.contributor.authorLima, Álvaro da Costapt_BR
dc.contributor.authorCampeiro, Joana D'Arcpt_BR
dc.contributor.authorMeurer, Ywllianept_BR
dc.contributor.authorTeixeira, Nathália Bernardespt_BR
dc.contributor.authorDuarte, Thiagopt_BR
dc.contributor.authorOliveira, Eduardo Brandtpt_BR
dc.contributor.authorPicolo, Giselept_BR
dc.contributor.authorGodinho, Rosely Oliveirapt_BR
dc.contributor.authorSilva, Regina Helenapt_BR
dc.contributor.authorHayashi, Mirian Akemi Furuiept_BR
dc.date.accessioned2020-07-09T21:21:46Z-
dc.date.available2020-07-09T21:21:46Z-
dc.date.issued2018pt_BR
dc.identifier.citationLima SC, Porta LC, Lima AC, Campeiro JD'A, Meurer Y, Teixeira NB, et al. Pharmacological characterization of crotamine effects on mice hind limb paralysis employing both ex vivo and in vivo assays: Insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal muscles. Plos Neglect. Trop. Dis.. 2018 Aug;12(8):e0006700. doi:10.1371/journal.pntd.0006700.pt_BR
dc.identifier.urihttps://repositorio.butantan.gov.br/handle/butantan/2593-
dc.description.abstractThe high medical importance of Crotalus snakes is unquestionable, as this genus is the second in frequency of ophidian accidents in many countries, including Brazil. With a relative less complex composition compared to other genera venoms, as those from the Bothrops genus, the Crotalus genus venom from South America is composed basically by the neurotoxin crotoxin (a phospholipase A2), the thrombin-like gyroxin (a serinoprotease), a very potent aggregating protein convulxin, and a myotoxic polypeptide named crotamine. Interestingly not all Crotalus snakes express crotamine, which was first described in early 50s due to its ability to immobilize animal hind limbs, contributing therefore to the physical immobilization of preys and representing an important advantage for the envenoming efficacy, and consequently, for the feeding and survival of these snakes in nature. Representing about 10–25% of the dry weight of the crude venom of crotamine-positive rattlesnakes, the polypeptide crotamine is also suggested to be of importance for antivenom therapy, although the contribution of this toxin to the main symptoms of envenoming process remains far unknown until now. Herein, we concomitantly performed in vitro and in vivo assays to show for the first time the dose-dependent response of crotamine-triggered hind limbs paralysis syndrome, up to now believed to be observable only at high (sub-lethal) concentrations of crotamine. In addition, ex vivo assay performed with isolated skeletal muscles allowed us to suggest here that compounds active on voltage-sensitive sodium and/or potassium ion channels could both affect the positive inotropic effect elicited by crotamine in isolated diaphragm, besides also affecting the hind limbs paralysis syndrome imposed by crotamine in vivo. By identifying the potential molecular targets of this toxin, our data may contribute to open new roads for translational studies aiming to improve the snakebite envenoming treatment in human. Interestingly, we also demonstrate that the intraplantal or intraperitoneal (ip) injections of crotamine in mice do not promote pain. Therefore, this work may also suggest the profitable utility of non-toxic analogs of crotamine as a potential tool for targeting voltage-gated ion channels in skeletal muscles, aiming its potential use in the therapy of neuromuscular dysfunctions and envenoming therapy.pt_BR
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)pt_BR
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt_BR
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt_BR
dc.format.extente0006700pt_BR
dc.language.isoEnglishpt_BR
dc.relation.ispartofPlos Neglected Tropical Diseasespt_BR
dc.rightsOpen Accesspt_BR
dc.titlePharmacological characterization of crotamine effects on mice hind limb paralysis employing both ex vivo and in vivo assays: insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal musclespt_BR
dc.typeArticlept_BR
dc.identifier.doi10.1371/journal.pntd.0006700pt_BR
dc.identifier.urlhttps://doi.org/10.1371/journal.pntd.0006700pt_BR
dc.contributor.externalUniversidade Federal de São Paulo (UNIFESP)¦¦Brasilpt_BR
dc.contributor.externalUniversidade Federal do Rio Grande do Norte (UFRN)¦¦Brasilpt_BR
dc.contributor.externalUniversidade de São Paulo (USP)¦¦Brasilpt_BR
dc.identifier.citationvolume12pt_BR
dc.identifier.citationissue8pt_BR
dc.relation.ispartofabbreviatedPlos Neglect Trop Dispt_BR
dc.identifier.citationabntv. 12, n. 8, e0006700, ago. 2018pt_BR
dc.identifier.citationvancouver2018 Aug;12(8):e0006700pt_BR
dc.contributor.butantanTeixeira, Nathália Bernardes|:Aluno|:LEDS - Laboratório de Dor e Sinalização|:pt_BR
dc.contributor.butantanPicolo, Gisele|:Pesquisador:Docente Permanente PPGTOX|:LEDS - Laboratório de Dor e Sinalização|:pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦311815/2012-0pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦475739/2013-2pt_BR
dc.sponsorship.butantanConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)¦¦39337/2016-0pt_BR
dc.sponsorship.butantanCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)¦¦pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2013/13392-4pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2015/07019-4pt_BR
dc.sponsorship.butantanFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)¦¦2017/02413-1pt_BR
dc.identifier.bvsccBR78.1pt_BR
dc.identifier.bvsdbIBProdpt_BR
dc.description.dbindexedYespt_BR
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