Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.

Detalhes bibliográficos
Autor(a) principal: Silva, Ingrid Kich da
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/19578
Resumo: Clioquinol (CQ) belongs to the class of anti-infective and antimicrobial agents. In the 1970s, CQ was withdrawn from the market due to reports of neurotoxicity in patients in Japan, and being associated with the manifestation of a neurodegenerative syndrome (SMON). Despite the exclusion of the drug for oral treatments, topical formulations for treating fungal and parasitic infections remained available. CQ is currently available as a topical antibiotic under the tradename Vioformi®. Given the potential reintroduction of oral QC formulations for novel indications, a better understanding of its toxicity is needed. This study intends to enhance our knowledge about the potential toxicity caused by CQ evaluating its effects on the embryonic development of zebrafish (Danio rerio). The embryos were exposed the concentrations of 0.1, 0.5, 1.0, 1.5 and 2.0 μg/ml of the CQ for 168 hours, evaluating the physiological, morphological and behavioral parameters. It was found that CQ exhibits a wide spectrum of toxicity and causes 100% mortality in the first 48 hours at concentrations of 1.5 and 2.0 μg/ml therefore; these concentrations were excluded from further evaluations. We observed a delay in hatching rate evaluated after 72 hours of exposure to 1 μg/ml; in addition, at the concentrations of 0.5 and 1.0 μg/ml, four main types of morphological abnormalities were observed. The exploratory behavior of the larvae was also examined in 7 dpf (days after fertilization) to determine if the exposure to CQ could alter the locomotion and orientation of the larvae. The behavior was evaluated only at the lowest CQ concentration tested in which the morphological alterations were not severe. Exposure of larva to CQ 0.1 μg/ml resulted in altered swimming patterns and it is suggested that the observed locomotor alterations may be associated with damage caused by CQ. In summary, this study is the first to demonstrate the potential embryotoxicity induced by CQ in zebrafish.
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spelling Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.Study of Clioquinol toxicity on embryonic development of zebrafish.AntimicrobianoZebrafishEmbriologiaEfeito tóxicoAntimicrobialZebrafishEmbryologyEmbryotoxicityCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAClioquinol (CQ) belongs to the class of anti-infective and antimicrobial agents. In the 1970s, CQ was withdrawn from the market due to reports of neurotoxicity in patients in Japan, and being associated with the manifestation of a neurodegenerative syndrome (SMON). Despite the exclusion of the drug for oral treatments, topical formulations for treating fungal and parasitic infections remained available. CQ is currently available as a topical antibiotic under the tradename Vioformi®. Given the potential reintroduction of oral QC formulations for novel indications, a better understanding of its toxicity is needed. This study intends to enhance our knowledge about the potential toxicity caused by CQ evaluating its effects on the embryonic development of zebrafish (Danio rerio). The embryos were exposed the concentrations of 0.1, 0.5, 1.0, 1.5 and 2.0 μg/ml of the CQ for 168 hours, evaluating the physiological, morphological and behavioral parameters. It was found that CQ exhibits a wide spectrum of toxicity and causes 100% mortality in the first 48 hours at concentrations of 1.5 and 2.0 μg/ml therefore; these concentrations were excluded from further evaluations. We observed a delay in hatching rate evaluated after 72 hours of exposure to 1 μg/ml; in addition, at the concentrations of 0.5 and 1.0 μg/ml, four main types of morphological abnormalities were observed. The exploratory behavior of the larvae was also examined in 7 dpf (days after fertilization) to determine if the exposure to CQ could alter the locomotion and orientation of the larvae. The behavior was evaluated only at the lowest CQ concentration tested in which the morphological alterations were not severe. Exposure of larva to CQ 0.1 μg/ml resulted in altered swimming patterns and it is suggested that the observed locomotor alterations may be associated with damage caused by CQ. In summary, this study is the first to demonstrate the potential embryotoxicity induced by CQ in zebrafish.O Clioquinol (CQ) pertence à classe dos agentes anti-infecciosos e antimicrobianos. Nos anos 70, o CQ foi retirado do mercado devido a relatos de neurotoxicidade em pacientes no Japão, e por estar associado à manifestação de uma síndrome neurodegenerativa (SMON). Apesar da exclusão do fármaco para tratamentos via oral, as formulações tópicas para tratamento de infecções fúngicas e parasitárias continuaram disponíveis. Atualmente, o CQ está disponível como antibiótico tópico sob o nome comercial Vioformio®. Dada a potencial reintrodução de formulações orais do CQ para novas indicações, uma melhor compreensão de sua toxicidade se faz necessária. Este estudo pretende aprofundar o conhecimento sobre a potencial toxicidade induzida pelo CQ avaliando seus efeitos sobre o desenvolvimento embrionário do peixe-zebra (Danio rerio). Os embriões foram expostos às concentrações de 0,5, 1,0, 1,5 e 2,0 μg/ml do CQ, durante 168 horas, avaliando-se ao final dos tratamentos parâmetros fisiológicos, morfológicos e comportamentais. Verificou-se que o CQ exibe um amplo espectro de toxicidade e que provoca 100% de mortalidade já nas primeiras 48 horas nas concentrações de 1,5 e 2,0 μg/ml. Além disso, observamos um atraso na taxa de eclosão avaliada após 72 horas da exposição à concentração de 1 μg/ml, além disso, nas concentrações de 0,5 e 1,0 μg/ml foram observados quatro principais tipos de anormalidades morfológicas. O comportamento exploratório das larvas também foi examinado em 7 dpf para determinar se a exposição ao CQ poderia alterar a locomoção e orientação das larvas. Os ensaios de comportamento foram avaliados somente na concentração de 0,1 μg/ml, na qual as alterações morfológicas não foram severas em relação às demais concentrações testadas. A exposição ao CQ nesta concentração foi capaz de alterar o padrão de natação das larvas, e com isso sugerimos que alterações locomotoras apresentadas pelas larvas podem estar associadas a danos causados pelo CQ durante o desenvolvimento embrio-larval. Em suma, este estudo demonstra de forma inédita a potencial embriotoxicidade induzida pelo CQ em peixe-zebra.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasFranco, Jeferson Luishttp://lattes.cnpq.br/1680065573338339Rosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056Trevisan, Rafaelhttp://lattes.cnpq.br/5809871783035231Silva, Ingrid Kich da2020-02-13T15:45:54Z2020-02-13T15:45:54Z2019-08-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/19578porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2020-02-14T06:00:38Zoai:repositorio.ufsm.br:1/19578Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2020-02-14T06:00:38Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
Study of Clioquinol toxicity on embryonic development of zebrafish.
title Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
spellingShingle Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
Silva, Ingrid Kich da
Antimicrobiano
Zebrafish
Embriologia
Efeito tóxico
Antimicrobial
Zebrafish
Embryology
Embryotoxicity
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
title_short Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
title_full Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
title_fullStr Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
title_full_unstemmed Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
title_sort Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
author Silva, Ingrid Kich da
author_facet Silva, Ingrid Kich da
author_role author
dc.contributor.none.fl_str_mv Franco, Jeferson Luis
http://lattes.cnpq.br/1680065573338339
Rosemberg, Denis Broock
http://lattes.cnpq.br/7713953979203056
Trevisan, Rafael
http://lattes.cnpq.br/5809871783035231
dc.contributor.author.fl_str_mv Silva, Ingrid Kich da
dc.subject.por.fl_str_mv Antimicrobiano
Zebrafish
Embriologia
Efeito tóxico
Antimicrobial
Zebrafish
Embryology
Embryotoxicity
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
topic Antimicrobiano
Zebrafish
Embriologia
Efeito tóxico
Antimicrobial
Zebrafish
Embryology
Embryotoxicity
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA
description Clioquinol (CQ) belongs to the class of anti-infective and antimicrobial agents. In the 1970s, CQ was withdrawn from the market due to reports of neurotoxicity in patients in Japan, and being associated with the manifestation of a neurodegenerative syndrome (SMON). Despite the exclusion of the drug for oral treatments, topical formulations for treating fungal and parasitic infections remained available. CQ is currently available as a topical antibiotic under the tradename Vioformi®. Given the potential reintroduction of oral QC formulations for novel indications, a better understanding of its toxicity is needed. This study intends to enhance our knowledge about the potential toxicity caused by CQ evaluating its effects on the embryonic development of zebrafish (Danio rerio). The embryos were exposed the concentrations of 0.1, 0.5, 1.0, 1.5 and 2.0 μg/ml of the CQ for 168 hours, evaluating the physiological, morphological and behavioral parameters. It was found that CQ exhibits a wide spectrum of toxicity and causes 100% mortality in the first 48 hours at concentrations of 1.5 and 2.0 μg/ml therefore; these concentrations were excluded from further evaluations. We observed a delay in hatching rate evaluated after 72 hours of exposure to 1 μg/ml; in addition, at the concentrations of 0.5 and 1.0 μg/ml, four main types of morphological abnormalities were observed. The exploratory behavior of the larvae was also examined in 7 dpf (days after fertilization) to determine if the exposure to CQ could alter the locomotion and orientation of the larvae. The behavior was evaluated only at the lowest CQ concentration tested in which the morphological alterations were not severe. Exposure of larva to CQ 0.1 μg/ml resulted in altered swimming patterns and it is suggested that the observed locomotor alterations may be associated with damage caused by CQ. In summary, this study is the first to demonstrate the potential embryotoxicity induced by CQ in zebrafish.
publishDate 2019
dc.date.none.fl_str_mv 2019-08-30
2020-02-13T15:45:54Z
2020-02-13T15:45:54Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufsm.br/handle/1/19578
url http://repositorio.ufsm.br/handle/1/19578
dc.language.iso.fl_str_mv por
language por
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.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Centro de Ciências Naturais e Exatas
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Brasil
Bioquímica
UFSM
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
Centro de Ciências Naturais e Exatas
dc.source.none.fl_str_mv reponame:Manancial - Repositório Digital da UFSM
instname:Universidade Federal de Santa Maria (UFSM)
instacron:UFSM
instname_str Universidade Federal de Santa Maria (UFSM)
instacron_str UFSM
institution UFSM
reponame_str Manancial - Repositório Digital da UFSM
collection Manancial - Repositório Digital da UFSM
repository.name.fl_str_mv Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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