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dc.contributor.CRUESPUNIVERSIDADE ESTADUAL DE CAMPINASpt_BR
dc.contributor.authorunicampOliveira, Rhaul de-
dc.typeArtigopt_BR
dc.titleIn vitro genotoxicity and in vivo subchronic evaluation of the anti-inflammatory pyrazole compound LQFM021pt_BR
dc.contributor.authorMoura, Soraia Santana de-
dc.contributor.authorÁvila, Renato Ivan de-
dc.contributor.authorBrito, Lara Barroso-
dc.contributor.authorOliveira, Rhaul de-
dc.contributor.authorOliveira, Gisele Augusto Rodrigues de-
dc.contributor.authorPazini, Francine-
dc.contributor.authorMenegatti, Ricardo-
dc.contributor.authorBatista, Aline Carvalho-
dc.contributor.authorGrisolia, Cesar Koppe-
dc.contributor.authorValadares, Marize Campos-
dc.subjectGenotoxicidadept_BR
dc.subject.otherlanguageGenotoxicitypt_BR
dc.description.abstractScientific evidences have highlighted 5-(1-(3-fluorophenyl)-1H-pyrazol-4-yl)-2H-tetrazole (LQFM021) as a promising anti-inflammatory, analgesic and antinociceptive agent due to its effects on peripheral opioid receptors associated with activation of the nitric oxide/cGMP/KATP pathway. Despite these important pharmacological findings, toxicity data of LQFM021 are scarce. Thus, this study investigated the in vitro genotoxicity of LQFM021 through cytokinesis-block micronucleus assay (OECD Nº 487/2014). Moreover, zebrafish model was used to assess the embryotoxicity potential of LQFM021 using fish embryo toxicity test (OECD Nº 236/2013) with extended exposure to evaluate subchronic larval development. In vivo subchronic toxicity of LQFM021 in rats (OECD Nº 407/2008) was also conducted. This compound at the lower concentrations tested (3.1 and 31 μg/mL) did not promote changes in micronuclei frequency in HepG2 cells. However, in the higher concentrations of LQFM021 (310 and 620 μg/mL) triggered a significant increase of micronucleated HepG2 cells, showing an alert signal of potential genotoxicity. Regarding the oral treatment of rats with LQFM021 (62.5, 125 or 250 mg/kg) for 28 days, the main findings showed that LQFM021 promoted renal and liver changes in a dose-dependent manner, being irreversible damage for kidneys while liver tissue showed a recovery after 14 days post treatment. Regarding embryotoxicity, although the lower concentrations used did not show toxicity, the concentration of LQFM021 (39.8 and 100 mg/L) promoted malformations in zebrafish embryo-larvae stage, in especial cardiac tissue changes. In conclusion, anti-inflammatory compound LQFM021 seems to have some limiting factors as a new therapeutic option to be used orally and in high repeated doses, related to those found in the non-steroidal anti-inflammatory drugs (NSAIDs)pt_BR
dc.relation.ispartofChemico-biological interactionspt_BR
dc.relation.ispartofabbreviationChem.-biol. interact.pt_BR
dc.publisher.cityLimerickpt_BR
dc.publisher.countryIrlandapt_BR
dc.publisherElsevierpt_BR
dc.date.issued2017-
dc.date.monthofcirculationNov.pt_BR
dc.language.isoengpt_BR
dc.description.volume277pt_BR
dc.description.firstpage185pt_BR
dc.description.lastpage194pt_BR
dc.rightsFechadopt_BR
dc.sourceWOSpt_BR
dc.identifier.issn0009-2797pt_BR
dc.identifier.eissn1872-7786pt_BR
dc.identifier.doi10.1016/j.cbi.2017.09.004pt_BR
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0009279717306932pt_BR
dc.description.sponsorshipCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESpt_BR
dc.description.sponsorshipCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQpt_BR
dc.description.sponsorshipFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE GOIÁS - FAPEGpt_BR
dc.description.sponsorshipFINANCIADORA DE ESTUDOS E PROJETOS - FINEPpt_BR
dc.description.sponsordocumentnumberSem informaçãopt_BR
dc.description.sponsordocumentnumberSem informaçãopt_BR
dc.description.sponsordocumentnumberSem informaçãopt_BR
dc.description.sponsordocumentnumberSem informaçãopt_BR
dc.date.available2021-03-10T17:56:04Z-
dc.date.accessioned2021-03-10T17:56:04Z-
dc.description.provenanceSubmitted by Thais de Brito Barroso (tbrito@unicamp.br) on 2021-03-10T17:56:04Z No. of bitstreams: 0. Added 1 bitstream(s) on 2021-09-02T14:26:01Z : No. of bitstreams: 1 000416216100022.pdf: 2666395 bytes, checksum: efeb24784f9a36b59ca827c3ae977c9b (MD5)en
dc.description.provenanceMade available in DSpace on 2021-03-10T17:56:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2017en
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/357427-
dc.contributor.departmentSem informaçãopt_BR
dc.contributor.unidadeFaculdade de Tecnologiapt_BR
dc.subject.keywordPyrazolept_BR
dc.subject.keywordMolecular hybridizationpt_BR
dc.subject.keywordZebrafishpt_BR
dc.subject.keywordSubchronic toxicitypt_BR
dc.subject.keywordAnti-inflammatory drugspt_BR
dc.identifier.source000416216100022pt_BR
dc.creator.orcid0000-0002-0272-3857pt_BR
dc.type.formArtigopt_BR
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