In Silico,In Vitro and In Vivo Toxicological Assessment of BPP-BrachyNH2, A Vasoactive Proline-Rich Oligopeptide from Brachycephalus ephippium |
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| Authors: | Daniel D. R. Arcanjo Ana Carolina Mafud Andreanne G. Vasconcelos José Couras da Silva-Filho Maurício P. M. Amaral Lucas M. Brito Marcelo P. Bemquerer Selma A. S. Kückelhaus Alexandra Plácido Cristina Delerue-Matos Nuno Vale Yvonne P. Mascarenhas Fernando Aécio A. Carvalho Aldeidia P. Oliveira José Roberto Souza Almeida Leite |
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| Affiliation: | 1.Núcleo de Pesquisa em Biodiversidade e Biotecnologia, BIOTEC, Campus Ministro Reis Velloso – CMRV,Universidade Federal do Piauí, UFPI,Parnaíba,Brazil;2.Núcleo de Pesquisas em Plantas Medicinais, NPPM,Universidade Federal do Piauí – UFPI,Teresina,Brazil;3.Instituto de Física de S?o Carlos – IFSC,Universidade de S?o Paulo – USP,S?o Carlos,Brazil;4.Laboratório de Espectrometria de Massa,EMBRAPA Recursos Genéticos e Biotecnologia,Brasília,Brazil;5.Area Morfologia, Faculdade de Medicina,Universidade de Brasília (UnB),Brasília,Brazil;6.REQUIMTE/LAQV,Instituto Superior de Engenharia do Instituto Politécnico do Porto,Porto,Portugal;7.UCIBIO/REQUIMTE, Departamento de Química e Bioquímica,Faculdade de Ciências da Universidade do Porto,Porto,Portugal |
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| Abstract: | BPP-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. |
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