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In Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippium

dc.contributor.authorArcanjo, Daniel D. R.
dc.contributor.authorMafud, Ana Carolina
dc.contributor.authorVasconcelos, Andreanne G.
dc.contributor.authorSilva-Filho, José Couras da
dc.contributor.authorAmaral, Maurício P. M.
dc.contributor.authorBrito, Lucas M.
dc.contributor.authorBemquerer, Marcelo P.
dc.contributor.authorKückelhaus, Selma A. S.
dc.contributor.authorPlácido, Alexandra
dc.contributor.authorDelerue-Matos, Cristina
dc.contributor.authorVale, Nuno
dc.contributor.authorMascarenhas, Yvonne P.
dc.contributor.authorCarvalho, Fernando Aécio A.
dc.contributor.authorOliveira, Aldeidia P.
dc.contributor.authorLeite, José Roberto Souza Almeida
dc.date.accessioned2019-04-17T14:39:01Z
dc.date.available2019-04-17T14:39:01Z
dc.date.issued2016
dc.description.abstractBPP-BrachyNH2 is a proline-rich oligopeptide (PRO) firstly identified in skin secretion of the frog Brachycephalus ephippium, which possess in vitro inhibitory activity of angiotensin-I converting enzyme (ACE) and endothelium-dependent vasorelaxant activity. Considering its potential application in the treatment of cardiovascular diseases, the present work assessed the toxicological profile of the BPP-BrachyNH2. The in silico toxicity prediction was performed from the best model obtained through the optimization of the FASTA query peptide. This prediction study revealed that BPP-BrachyNH2 induced high predicted LD50 values for both humans and rats, and then is well-tolerated in the recommended range. The MTT assay was applied for the in vitro cytotoxic evaluation in murine macrophages. In this assay, a decrease of cell viability was not observed. The in vivo acute toxicological study was performed after the intraperitoneal administration of BPP-BrachyNH2 at doses of 5 and 50 mg/kg. After intraperitoneal administration, no death, alterations in behavioral parameters or weight gain curve was observed, as well as none in the serum biochemical parameters, and gross pathological and histopathological analyses. These observations demonstrates an acceptable safety profile for BPP-BrachyNH2, leading towards further studies focused on investigation of pharmacological and therapeutical applications for this peptide.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.doi10.1007/s10989-016-9564-2pt_PT
dc.identifier.issn1573-3149
dc.identifier.issn1573-3904
dc.identifier.urihttp://hdl.handle.net/10400.22/13629
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.relation.publisherversionhttps://link.springer.com/article/10.1007%2Fs10989-016-9564-2pt_PT
dc.subjectCytotoxicitypt_PT
dc.subjectMTTpt_PT
dc.subjectIn silicopt_PT
dc.subjectpkCSMpt_PT
dc.subjectProline-rich oligopeptidept_PT
dc.subjectToxicologicalpt_PT
dc.titleIn Silico, In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippiumpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage331pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage323pt_PT
oaire.citation.titleInternational Journal of Peptide Research and Therapeuticspt_PT
oaire.citation.volume23pt_PT
person.familyNameDelerue-Matos
person.givenNameCristina
person.identifier.ciencia-id9A1A-43FB-5C27
person.identifier.orcid0000-0002-3924-776X
person.identifier.ridD-4990-2013
person.identifier.scopus-author-id6603741848
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication09f6a7bd-2f15-42b0-adc5-04bd22210519
relation.isAuthorOfPublication.latestForDiscovery09f6a7bd-2f15-42b0-adc5-04bd22210519

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