Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional Manancial 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 In the 1970s, CQ was withdrawn from the market due to reports of neurotoxicity in patients in Japan, and being associated with the manifestation of a neurodegenerative syndrome (SMON).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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2020-02-13T15:45:54Z2020-02-13T15:45:54Z2019-08-30http://repositorio.ufsm.br/handle/1/19578Clioquinol (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.porUniversidade Federal de Santa MariaCentro de Ciências Naturais e ExatasPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBrasilBioquímicaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAntimicrobianoZebrafishEmbriologiaEfeito tóxicoAntimicrobialZebrafishEmbryologyEmbryotoxicityCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEstudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra.Study of Clioquinol toxicity on embryonic development of zebrafish.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisFranco, Jeferson Luishttp://lattes.cnpq.br/1680065573338339Rosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056Trevisan, Rafaelhttp://lattes.cnpq.br/5809871783035231http://lattes.cnpq.br/3799682858372218Silva, Ingrid Kich da20080000000260016ea12f1-12c6-4435-a98c-cdeb5f7d1c5981b7dbab-a8c9-4946-a7c8-4acf4fc6b512c677f64b-5cc5-4b69-a688-583d9209b1b08904f9ef-e743-4390-bbc6-cfff26489a92reponame:Repositório Institucional Manancial UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGCBBT_2019_SILVA_INGRID.pdfDIS_PPGCBBT_2019_SILVA_INGRID.pdfDissertação de Mestradoapplication/pdf2605930http://repositorio.ufsm.br/bitstream/1/19578/1/DIS_PPGCBBT_2019_SILVA_INGRID.pdf53593264cecc421bc5fb9fefec794a79MD51LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Estudo da toxicidade do Clioquinol sobre o desenvolvimento embrionário do peixe-zebra. |
dc.title.alternative.eng.fl_str_mv |
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.advisor1.fl_str_mv |
Franco, Jeferson Luis |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1680065573338339 |
dc.contributor.referee1.fl_str_mv |
Rosemberg, Denis Broock |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/7713953979203056 |
dc.contributor.referee2.fl_str_mv |
Trevisan, Rafael |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/5809871783035231 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3799682858372218 |
dc.contributor.author.fl_str_mv |
Silva, Ingrid Kich da |
contributor_str_mv |
Franco, Jeferson Luis Rosemberg, Denis Broock Trevisan, Rafael |
dc.subject.por.fl_str_mv |
Antimicrobiano Zebrafish Embriologia Efeito tóxico |
topic |
Antimicrobiano Zebrafish Embriologia Efeito tóxico Antimicrobial Zebrafish Embryology Embryotoxicity CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Antimicrobial Zebrafish Embryology Embryotoxicity |
dc.subject.cnpq.fl_str_mv |
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.issued.fl_str_mv |
2019-08-30 |
dc.date.accessioned.fl_str_mv |
2020-02-13T15:45:54Z |
dc.date.available.fl_str_mv |
2020-02-13T15:45:54Z |
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info:eu-repo/semantics/publishedVersion |
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masterThesis |
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publishedVersion |
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http://repositorio.ufsm.br/handle/1/19578 |
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http://repositorio.ufsm.br/handle/1/19578 |
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por |
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por |
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200800000002 |
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600 |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
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Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
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openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
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UFSM |
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Brasil |
dc.publisher.department.fl_str_mv |
Bioquímica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Centro de Ciências Naturais e Exatas |
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