Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo
Ano de defesa: | 2021 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , , , , |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Goiás
|
Programa de Pós-Graduação: |
Programa de Pós-graduação em Ciências Farmacêuticas (FF)
|
Departamento: |
Faculdade de Farmácia - FF (RG)
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.bc.ufg.br/tede/handle/tede/12366 |
Resumo: | Zebrafish (Danio rerio) early-life stages offer a complex and multicellular system integrating various tissues and differentiation processes. In addition, the zebrafish embryos are structurally and functionally similar to vertebrates, including humans. The acute toxicity test with zebrafish embryos and larvae is already worldwide recognized as an alternative model for ecotoxicological assessment, but it is not include in normative of the Council fot the Control of Animal Experimentation (CONCEA), wich recognize the use of alternative methods validated in research activities in Brazil. This organism model can filling the gap between conventional in vitro and in vivo tests for extrapolation of data for humans, the present study aimed to assess the acute toxicity of substances with different Global Harmonization System (GHS) categories using zebrafish early-life stage to determine LC50 values and compared with in vivo (LD50) acute oral toxicity data from literature, in order to generate a model to prediction acute oral toxicity. This prediction model was evaluated by the application of a drug candidate (LQFM 021). Fifteen substances were evaluated by Fish Embryo Acute Toxicity (FET) test (OECD 236). Parameter evaluated was lethal and sublethal effects after 96 h of exposure. A linear regression- model using the log-transformed of the LC50 values and LD50 was generated for the estimated of LD50 from LC50 values. This model resulted in the following equation Log LD50 (mg/kg) = 0.5749 x log LC50 (mg/L) + 1.284. The method domain of application was 53.33% and the R2 was 0,66. Sublethal effects indicate that substances more toxic presented more abnormalities. The DL50 predicted with FET testing LQFM 021, which classified as category 4 in GHS acute oral systemic toxicity assessment, was of 408.52 mg/kg, which also classified as Category 4. In this work, Quantitative Activity-Activity Relationship (QAAR) models were also developed, based on the data obtained in the FET test with zebrafish. This model using seven toxicological descriptors generated statistically predictive models with R2 values ranging from 0.80 to 0.95 and in combination with the Random Forest method it presented the best performance in the prediction of acute oral toxicity in vivo. Therefore, our results suggest that early-life stages of zebrafish could be at least a refinement in the sense of the principles of the 3R’s to predict acute oral toxicity in vivo, being as an intermediary in the preclinical evaluation between in vitro and in vitro. |
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Oliveira, Gisele Augusto Rodrigues dehttp://lattes.cnpq.br/6221735418479539Valadares, Marize Camposhttp://lattes.cnpq.br/6157755243167018Oliveira, Danielle Palma deRocha, Matheus LavorentiFerreira, Monica Valdyrce dos Anjos LopesAlves, Vinícius de MedeirosValadares, Marize Camposhttp://lattes.cnpq.br/4214326598221702Prado, Lara Barroso Brito2022-10-11T11:46:14Z2022-10-11T11:46:14Z2021-02-11BRITO, L. B. Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo. 2021. 91 f. Tese (Doutorado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2021.http://repositorio.bc.ufg.br/tede/handle/tede/12366Zebrafish (Danio rerio) early-life stages offer a complex and multicellular system integrating various tissues and differentiation processes. In addition, the zebrafish embryos are structurally and functionally similar to vertebrates, including humans. The acute toxicity test with zebrafish embryos and larvae is already worldwide recognized as an alternative model for ecotoxicological assessment, but it is not include in normative of the Council fot the Control of Animal Experimentation (CONCEA), wich recognize the use of alternative methods validated in research activities in Brazil. This organism model can filling the gap between conventional in vitro and in vivo tests for extrapolation of data for humans, the present study aimed to assess the acute toxicity of substances with different Global Harmonization System (GHS) categories using zebrafish early-life stage to determine LC50 values and compared with in vivo (LD50) acute oral toxicity data from literature, in order to generate a model to prediction acute oral toxicity. This prediction model was evaluated by the application of a drug candidate (LQFM 021). Fifteen substances were evaluated by Fish Embryo Acute Toxicity (FET) test (OECD 236). Parameter evaluated was lethal and sublethal effects after 96 h of exposure. A linear regression- model using the log-transformed of the LC50 values and LD50 was generated for the estimated of LD50 from LC50 values. This model resulted in the following equation Log LD50 (mg/kg) = 0.5749 x log LC50 (mg/L) + 1.284. The method domain of application was 53.33% and the R2 was 0,66. Sublethal effects indicate that substances more toxic presented more abnormalities. The DL50 predicted with FET testing LQFM 021, which classified as category 4 in GHS acute oral systemic toxicity assessment, was of 408.52 mg/kg, which also classified as Category 4. In this work, Quantitative Activity-Activity Relationship (QAAR) models were also developed, based on the data obtained in the FET test with zebrafish. This model using seven toxicological descriptors generated statistically predictive models with R2 values ranging from 0.80 to 0.95 and in combination with the Random Forest method it presented the best performance in the prediction of acute oral toxicity in vivo. Therefore, our results suggest that early-life stages of zebrafish could be at least a refinement in the sense of the principles of the 3R’s to predict acute oral toxicity in vivo, being as an intermediary in the preclinical evaluation between in vitro and in vitro.O estágio embrio-larval de zebrafish (Danio rerio) oferece um sistema complexo e multicelular que integra vários tecidos e processos de diferenciação. Além disso, os embriões de zebrafish são estrutural e funcionalmente semelhantes aos vertebrados, incluindo os humanos. O teste de toxicidade aguda com embriões e larvas de zebrafish já é uma abordagem alternativa reconhecida mundialmente para a avaliação ecotoxicológica, porém não está incluído nas normativas do Conselho Nacional de Controle de Experimentação Animal (CONCEA), as quais reconhecem o uso de métodos alternativos em atividades de pesquisa validados no Brasil. Considerando que este modelo pode preencher a lacuna entre os testes convencionais in vitro e in vivo para extrapolação de dados para humanos, o presente trabalho teve como objetivo avaliar a toxicidade aguda de substâncias com diferentes categorias no Sistema Global de Harmonização (GHS), usando o estágio embrio-larval de zebrafish para determinar os valores de CL50 e compará-los com dados in vivo (DL50) da literatura, a fim de gerar um modelo alternativo para predição da toxicidade oral aguda em roedores. Este modelo de predição foi avaliado pela aplicação de um candidato a fármaco (LQFM 021). Para tanto, 15 substâncias foram avaliadas utilizando o Fish Embryo Acute Toxicity (FET) Test (OECD 236). Os parâmetros avaliados foram os efeitos letais e subletais de cada substância e do LQFM 021, após 96 h de exposição. Um modelo de regressão linear usando os valores na escala logarítmica de CL50 e DL50 foi gerado para a estimar a DL50 a partir dos valores CL50 do teste de toxicidade aguda com zebrafish. Este modelo resultou na seguinte equação: Log DL50 (mg/kg) = 0,5749 x log CL50 (mg/L) + 1,284. O domínio de aplicação do método avaliado foi de 53,33% e o valor de R2 foi de 0,66. Em relação aos efeitos subletais, as substâncias categorizadas como mais tóxicas no GHS foram as que apresentaram mais anormalidades no desenvolvimento. A DL50 de predição do protótipo a fármaco LQFM 021, utilizando o teste FET, o qual é classificado como categoria 4 no GHS para toxicidade sistêmica oral aguda, foi de 408,52 mg/kg, ou seja, manteve- se classificado como categoria 4. Nesse trabalho também foi desenvolvido modelos de Relação Quantitativa Atividade-Atividade (QAAR), a partir dos dados obtidos no teste FET com zebrafish. Esse modelo utilizando sete descritores toxicológicos gerou modelos estatisticamente preditivos com valores de R2 variando entre 0,80 a 0,95 e em combinação com o método Random Forest apresentou o melhor desempenho na predição toxicidade oral aguda in vivo. Portanto nossos resultados sugerem que os estágios embrio-larvais de zebrafish poderia ser pelo menos um refinamento no sentido dos princípios de 3R’s para predizer a toxicidade oral aguda in vivo, se apresentando como um intermediário na avaliação pré-clínica entre os ensaios in vitro e in vivo.Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2022-10-10T11:34:36Z No. of bitstreams: 2 Tese - Lara Barroso Brito Prado - 2021.pdf: 9815570 bytes, checksum: 987614fef2dc13b84d652b4d36853469 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2022-10-11T11:46:14Z (GMT) No. of bitstreams: 2 Tese - Lara Barroso Brito Prado - 2021.pdf: 9815570 bytes, checksum: 987614fef2dc13b84d652b4d36853469 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5)Made available in DSpace on 2022-10-11T11:46:14Z (GMT). No. of bitstreams: 2 Tese - Lara Barroso Brito Prado - 2021.pdf: 9815570 bytes, checksum: 987614fef2dc13b84d652b4d36853469 (MD5) license_rdf: 805 bytes, checksum: 4460e5956bc1d1639be9ae6146a50347 (MD5) Previous issue date: 2021-02-11Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqporUniversidade Federal de GoiásPrograma de Pós-graduação em Ciências Farmacêuticas (FF)UFGBrasilFaculdade de Farmácia - FF (RG)Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessZebrafishToxicidade oral agudaDL50Sistema Global de HarmonizaçãoQAARZebrafishAcute oral toxicityDL50Alternative-testing methodsGlobal Harmonisation SystemQAARCIENCIAS HUMANAS::FILOSOFIA::ETICAOs estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivoZebrafish early-life stage as an alternative model to predict acute oral toxicity in vivoinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis27500500500500225320reponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8805http://repositorio.bc.ufg.br/tede/bitstreams/5c42cfae-ebe0-45de-92bc-dece8b365276/download4460e5956bc1d1639be9ae6146a50347MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.bc.ufg.br/tede/bitstreams/313c0a63-8704-458a-ac9b-2295a10a3317/download8a4605be74aa9ea9d79846c1fba20a33MD51ORIGINALTese - Lara Barroso Brito Prado - 2021.pdfTese - Lara Barroso Brito Prado - 2021.pdfapplication/pdf9815570http://repositorio.bc.ufg.br/tede/bitstreams/205136d7-4e58-421a-8949-60d1d8045416/download987614fef2dc13b84d652b4d36853469MD53tede/123662022-10-11 08:46:14.508http://creativecommons.org/licenses/by-nc-nd/4.0/Attribution-NonCommercial-NoDerivatives 4.0 Internationalopen.accessoai:repositorio.bc.ufg.br:tede/12366http://repositorio.bc.ufg.br/tedeRepositório InstitucionalPUBhttp://repositorio.bc.ufg.br/oai/requesttasesdissertacoes.bc@ufg.bropendoar:2022-10-11T11:46:14Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)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 |
dc.title.pt_BR.fl_str_mv |
Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo |
dc.title.alternative.eng.fl_str_mv |
Zebrafish early-life stage as an alternative model to predict acute oral toxicity in vivo |
title |
Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo |
spellingShingle |
Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo Prado, Lara Barroso Brito Zebrafish Toxicidade oral aguda DL50 Sistema Global de Harmonização QAAR Zebrafish Acute oral toxicity DL50 Alternative-testing methods Global Harmonisation System QAAR CIENCIAS HUMANAS::FILOSOFIA::ETICA |
title_short |
Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo |
title_full |
Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo |
title_fullStr |
Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo |
title_full_unstemmed |
Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo |
title_sort |
Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo |
author |
Prado, Lara Barroso Brito |
author_facet |
Prado, Lara Barroso Brito |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Oliveira, Gisele Augusto Rodrigues de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6221735418479539 |
dc.contributor.advisor-co1.fl_str_mv |
Valadares, Marize Campos |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/6157755243167018 |
dc.contributor.referee1.fl_str_mv |
Oliveira, Danielle Palma de |
dc.contributor.referee2.fl_str_mv |
Rocha, Matheus Lavorenti |
dc.contributor.referee3.fl_str_mv |
Ferreira, Monica Valdyrce dos Anjos Lopes |
dc.contributor.referee4.fl_str_mv |
Alves, Vinícius de Medeiros |
dc.contributor.referee5.fl_str_mv |
Valadares, Marize Campos |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4214326598221702 |
dc.contributor.author.fl_str_mv |
Prado, Lara Barroso Brito |
contributor_str_mv |
Oliveira, Gisele Augusto Rodrigues de Valadares, Marize Campos Oliveira, Danielle Palma de Rocha, Matheus Lavorenti Ferreira, Monica Valdyrce dos Anjos Lopes Alves, Vinícius de Medeiros Valadares, Marize Campos |
dc.subject.por.fl_str_mv |
Zebrafish Toxicidade oral aguda DL50 Sistema Global de Harmonização QAAR |
topic |
Zebrafish Toxicidade oral aguda DL50 Sistema Global de Harmonização QAAR Zebrafish Acute oral toxicity DL50 Alternative-testing methods Global Harmonisation System QAAR CIENCIAS HUMANAS::FILOSOFIA::ETICA |
dc.subject.eng.fl_str_mv |
Zebrafish Acute oral toxicity DL50 Alternative-testing methods Global Harmonisation System QAAR |
dc.subject.cnpq.fl_str_mv |
CIENCIAS HUMANAS::FILOSOFIA::ETICA |
description |
Zebrafish (Danio rerio) early-life stages offer a complex and multicellular system integrating various tissues and differentiation processes. In addition, the zebrafish embryos are structurally and functionally similar to vertebrates, including humans. The acute toxicity test with zebrafish embryos and larvae is already worldwide recognized as an alternative model for ecotoxicological assessment, but it is not include in normative of the Council fot the Control of Animal Experimentation (CONCEA), wich recognize the use of alternative methods validated in research activities in Brazil. This organism model can filling the gap between conventional in vitro and in vivo tests for extrapolation of data for humans, the present study aimed to assess the acute toxicity of substances with different Global Harmonization System (GHS) categories using zebrafish early-life stage to determine LC50 values and compared with in vivo (LD50) acute oral toxicity data from literature, in order to generate a model to prediction acute oral toxicity. This prediction model was evaluated by the application of a drug candidate (LQFM 021). Fifteen substances were evaluated by Fish Embryo Acute Toxicity (FET) test (OECD 236). Parameter evaluated was lethal and sublethal effects after 96 h of exposure. A linear regression- model using the log-transformed of the LC50 values and LD50 was generated for the estimated of LD50 from LC50 values. This model resulted in the following equation Log LD50 (mg/kg) = 0.5749 x log LC50 (mg/L) + 1.284. The method domain of application was 53.33% and the R2 was 0,66. Sublethal effects indicate that substances more toxic presented more abnormalities. The DL50 predicted with FET testing LQFM 021, which classified as category 4 in GHS acute oral systemic toxicity assessment, was of 408.52 mg/kg, which also classified as Category 4. In this work, Quantitative Activity-Activity Relationship (QAAR) models were also developed, based on the data obtained in the FET test with zebrafish. This model using seven toxicological descriptors generated statistically predictive models with R2 values ranging from 0.80 to 0.95 and in combination with the Random Forest method it presented the best performance in the prediction of acute oral toxicity in vivo. Therefore, our results suggest that early-life stages of zebrafish could be at least a refinement in the sense of the principles of the 3R’s to predict acute oral toxicity in vivo, being as an intermediary in the preclinical evaluation between in vitro and in vitro. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-02-11 |
dc.date.accessioned.fl_str_mv |
2022-10-11T11:46:14Z |
dc.date.available.fl_str_mv |
2022-10-11T11:46:14Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
BRITO, L. B. Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo. 2021. 91 f. Tese (Doutorado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2021. |
dc.identifier.uri.fl_str_mv |
http://repositorio.bc.ufg.br/tede/handle/tede/12366 |
identifier_str_mv |
BRITO, L. B. Os estágios iniciais do desenvolvimento do zebrafish como modelo alternativo para predizer a toxicidade oral aguda in vivo. 2021. 91 f. Tese (Doutorado em Ciências Farmacêuticas) - Universidade Federal de Goiás, Goiânia, 2021. |
url |
http://repositorio.bc.ufg.br/tede/handle/tede/12366 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.program.fl_str_mv |
27 |
dc.relation.confidence.fl_str_mv |
500 500 500 500 |
dc.relation.department.fl_str_mv |
22 |
dc.relation.cnpq.fl_str_mv |
532 |
dc.relation.sponsorship.fl_str_mv |
0 |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.publisher.program.fl_str_mv |
Programa de Pós-graduação em Ciências Farmacêuticas (FF) |
dc.publisher.initials.fl_str_mv |
UFG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Faculdade de Farmácia - FF (RG) |
publisher.none.fl_str_mv |
Universidade Federal de Goiás |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFG instname:Universidade Federal de Goiás (UFG) instacron:UFG |
instname_str |
Universidade Federal de Goiás (UFG) |
instacron_str |
UFG |
institution |
UFG |
reponame_str |
Repositório Institucional da UFG |
collection |
Repositório Institucional da UFG |
bitstream.url.fl_str_mv |
http://repositorio.bc.ufg.br/tede/bitstreams/5c42cfae-ebe0-45de-92bc-dece8b365276/download http://repositorio.bc.ufg.br/tede/bitstreams/313c0a63-8704-458a-ac9b-2295a10a3317/download http://repositorio.bc.ufg.br/tede/bitstreams/205136d7-4e58-421a-8949-60d1d8045416/download |
bitstream.checksum.fl_str_mv |
4460e5956bc1d1639be9ae6146a50347 8a4605be74aa9ea9d79846c1fba20a33 987614fef2dc13b84d652b4d36853469 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFG - Universidade Federal de Goiás (UFG) |
repository.mail.fl_str_mv |
tasesdissertacoes.bc@ufg.br |
_version_ |
1798045069129809920 |