Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans
Ano de defesa: | 2023 |
---|---|
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 Santa Maria
Centro de Ciências Naturais e Exatas |
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
Brasil
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/30790 |
Resumo: | Organic solvents are many used in industrial processes, among these solvents; we highlight the group benzene, toluene, ethylbenzene, and xylenes (BTEX), which are mainly emitted through industrial processes, but also by fossil fuel combustion. Exposures to these solvents occur mainly in two manners: intentional (drug abuse) or unintentional (environmental and occupational settings). In a context of abuse, the inhalation of toluene stands out, using glue shoes; whereas in non-intentional exposure, the contact occurs by BTEX mixture in the environment, and both exposures cause toxic effects to the organism, however, the specificity of the mechanisms involved is little explored. Based on this, our study sought to mimetize two exposure scenarios: using toluene, and simulating levels close to intentional use, and the BTEX mixture, simulating lower than occupational permissive levels, and investigating the long-term effects using the Caenorhabditis elegans model. The exposures were performed in a chamber by airborne methodology in a system applied to volatile compounds, and in the first scenario (intentional), we observed that exposure to toluene caused damage to dopaminergic neurons, locomotor and behavioral deficits associated with dopaminergic signaling, and also, using ex vivo/in vitro/in silico methodologies, it was seen that toluene possibly acts by inhibition of mitochondrial complex I, then, generates a mitochondrial dysfunction resulting in the outcome of neuronal death. In relation to the BTEX scenario, we observed that exposures to mixture, at permissive regulatory levels, generate an extensive deficit in nematode mobility, mitochondrial dysfunction, pigments accumulation and neuronal abnormalities, that together, using an only standardized index are correlated with loss of healthspan, as well as early aging. Together these findings, can established a possible new mechanism of toluene neurotoxicity, the mitochondrial dysfunction. And, furthermore, we reinforce the importance of investigation the role of mixtures, since regulatory levels are established only for the isolated agent, however, here it was observed that at permissive levels, the BTEX mixture generated long-term and irreversible effects. |
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2023-12-04T19:48:47Z2023-12-04T19:48:47Z2023-10-30http://repositorio.ufsm.br/handle/1/30790Organic solvents are many used in industrial processes, among these solvents; we highlight the group benzene, toluene, ethylbenzene, and xylenes (BTEX), which are mainly emitted through industrial processes, but also by fossil fuel combustion. Exposures to these solvents occur mainly in two manners: intentional (drug abuse) or unintentional (environmental and occupational settings). In a context of abuse, the inhalation of toluene stands out, using glue shoes; whereas in non-intentional exposure, the contact occurs by BTEX mixture in the environment, and both exposures cause toxic effects to the organism, however, the specificity of the mechanisms involved is little explored. Based on this, our study sought to mimetize two exposure scenarios: using toluene, and simulating levels close to intentional use, and the BTEX mixture, simulating lower than occupational permissive levels, and investigating the long-term effects using the Caenorhabditis elegans model. The exposures were performed in a chamber by airborne methodology in a system applied to volatile compounds, and in the first scenario (intentional), we observed that exposure to toluene caused damage to dopaminergic neurons, locomotor and behavioral deficits associated with dopaminergic signaling, and also, using ex vivo/in vitro/in silico methodologies, it was seen that toluene possibly acts by inhibition of mitochondrial complex I, then, generates a mitochondrial dysfunction resulting in the outcome of neuronal death. In relation to the BTEX scenario, we observed that exposures to mixture, at permissive regulatory levels, generate an extensive deficit in nematode mobility, mitochondrial dysfunction, pigments accumulation and neuronal abnormalities, that together, using an only standardized index are correlated with loss of healthspan, as well as early aging. Together these findings, can established a possible new mechanism of toluene neurotoxicity, the mitochondrial dysfunction. And, furthermore, we reinforce the importance of investigation the role of mixtures, since regulatory levels are established only for the isolated agent, however, here it was observed that at permissive levels, the BTEX mixture generated long-term and irreversible effects.Os solventes orgânicos são muito utilizados em processos industriais. Dentre estes solventes destacamos o grupo benzeno, tolueno, etilbenzeno e xilenos (BTEX), que são principalmente emitidos via processos industriais, mas também via queima de combustíveis fósseis. As exposições a estes solventes podem ocorrer principalmente de duas formas: intencional (droga de abuso) ou não intencional (ambiental ou ocupacional). Em um contexto de abuso, destaca-se a inalação do tolueno, utilizado na cola de sapato; já em exposições não intencionais, o contato ocorre via mistura BTEX pelo ambiente. Ambas as exposições acarretam efeitos tóxicos ao organismo, entretanto, a especificidade dos mecanismos envolvidos é pouco explorada. Baseado nisso, nosso estudo buscou mimetizar dois cenários de exposição: utilizando o tolueno isolado, simulando níveis próximos do uso intencional, e a mistura BTEX, simulando níveis menores dos permissivos no ar ocupacional, a fim de investigar os efeitos a longo prazo da mistura utilizando o modelo Caenorhabditis elegans. As exposições foram realizadas pelo ar em um sistema desenvolvido para exposição a compostos voláteis, e no primeiro cenário (intencional), observamos que a exposição ao tolueno resultou em dano aos neurônios dopaminérgicos, o que acarretou déficits locomotores e de comportamentos associados à sua sinalização. Além disso, utilizando metodologias ex vivo/in vitro/in silico, foi observado que o tolueno atua possivelmente via inibição do complexo I mitocondrial, o que gera uma disfunção mitocondrial ocasionando no desfecho de morte neuronal. Em relação ao cenário de exposição ao BTEX, foi possível observar que as exposições à mistura por 7 dias, mesmo que em níveis regulatórios permissivos, geram extenso déficit na mobilidade dos vermes, disfunção mitocondrial, acúmulo de pigmentos e danos neuronais, que em conjunto, via padronização de um índice único, se correlacionam com perda da qualidade de vida, caracterizando no envelhecimento precoce do organismo como um todo. Tais danos permaneceram 3 dias após a retirada da exposição. Diante de tais achados, podemos estabelecer um possível mecanismo de neurotoxicidade do tolueno, via disfunção mitocondrial. Além disso, reforçamos a importância da investigação do papel das misturas, uma vez que os níveis regulatórios estão estabelecidos apenas para o agente isolado, entretanto, foi observado que em níveis permissivos, a mistura BTEX gerou efeitos em longo prazo e de maneira irreversível em C. elegans.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade 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/openAccessMisturaPoluiçãoNeurotoxicidadeMitocôndriaSolventesMixturePollutionNeurotoxicityMitochondriaSolventsCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAvaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegansNeurobehavioral, mitochondrial, and aging evaluation after exposure to volatile organic compounds (VOCs) on Caenorhabditis elegansinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisÁvila, Daiana Silva dehttp://lattes.cnpq.br/4355211015887363Soares, Félix Alexandre AntunesFarina, MarceloBrucker, NatáliaSilva Júnior, Flavio Manoel Rodrigues daMoro, Vania Luciahttp://lattes.cnpq.br/1578669511184178Soares, Marcell Valandro200800000002600600600600600600600600dc8d4adf-bf4d-4497-86e6-4b824c8334a3165fbc62-0b38-4365-9beb-9c1ae4f67674d51c3c49-cc06-4b2f-b7fd-4d213a59b3395dd23b6c-62c2-4151-9273-82b3c73a45197e1d71bf-4010-48ae-bd49-256dee844c6deb8eb03a-f93c-48cb-a1e0-84e76eb8960c37d5bf29-7de1-44e4-98a8-902ac0fce7b3reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMLICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv |
Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans |
dc.title.alternative.eng.fl_str_mv |
Neurobehavioral, mitochondrial, and aging evaluation after exposure to volatile organic compounds (VOCs) on Caenorhabditis elegans |
title |
Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans |
spellingShingle |
Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans Soares, Marcell Valandro Mistura Poluição Neurotoxicidade Mitocôndria Solventes Mixture Pollution Neurotoxicity Mitochondria Solvents CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans |
title_full |
Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans |
title_fullStr |
Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans |
title_full_unstemmed |
Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans |
title_sort |
Avaliação neurocomportamental, mitocondrial e do envelhecimento após exposição a compostos orgânicos voláteis (COVs) em Caenorhabditis elegans |
author |
Soares, Marcell Valandro |
author_facet |
Soares, Marcell Valandro |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Ávila, Daiana Silva de |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/4355211015887363 |
dc.contributor.advisor-co1.fl_str_mv |
Soares, Félix Alexandre Antunes |
dc.contributor.referee1.fl_str_mv |
Farina, Marcelo |
dc.contributor.referee2.fl_str_mv |
Brucker, Natália |
dc.contributor.referee3.fl_str_mv |
Silva Júnior, Flavio Manoel Rodrigues da |
dc.contributor.referee4.fl_str_mv |
Moro, Vania Lucia |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1578669511184178 |
dc.contributor.author.fl_str_mv |
Soares, Marcell Valandro |
contributor_str_mv |
Ávila, Daiana Silva de Soares, Félix Alexandre Antunes Farina, Marcelo Brucker, Natália Silva Júnior, Flavio Manoel Rodrigues da Moro, Vania Lucia |
dc.subject.por.fl_str_mv |
Mistura Poluição Neurotoxicidade Mitocôndria Solventes |
topic |
Mistura Poluição Neurotoxicidade Mitocôndria Solventes Mixture Pollution Neurotoxicity Mitochondria Solvents CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Mixture Pollution Neurotoxicity Mitochondria Solvents |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Organic solvents are many used in industrial processes, among these solvents; we highlight the group benzene, toluene, ethylbenzene, and xylenes (BTEX), which are mainly emitted through industrial processes, but also by fossil fuel combustion. Exposures to these solvents occur mainly in two manners: intentional (drug abuse) or unintentional (environmental and occupational settings). In a context of abuse, the inhalation of toluene stands out, using glue shoes; whereas in non-intentional exposure, the contact occurs by BTEX mixture in the environment, and both exposures cause toxic effects to the organism, however, the specificity of the mechanisms involved is little explored. Based on this, our study sought to mimetize two exposure scenarios: using toluene, and simulating levels close to intentional use, and the BTEX mixture, simulating lower than occupational permissive levels, and investigating the long-term effects using the Caenorhabditis elegans model. The exposures were performed in a chamber by airborne methodology in a system applied to volatile compounds, and in the first scenario (intentional), we observed that exposure to toluene caused damage to dopaminergic neurons, locomotor and behavioral deficits associated with dopaminergic signaling, and also, using ex vivo/in vitro/in silico methodologies, it was seen that toluene possibly acts by inhibition of mitochondrial complex I, then, generates a mitochondrial dysfunction resulting in the outcome of neuronal death. In relation to the BTEX scenario, we observed that exposures to mixture, at permissive regulatory levels, generate an extensive deficit in nematode mobility, mitochondrial dysfunction, pigments accumulation and neuronal abnormalities, that together, using an only standardized index are correlated with loss of healthspan, as well as early aging. Together these findings, can established a possible new mechanism of toluene neurotoxicity, the mitochondrial dysfunction. And, furthermore, we reinforce the importance of investigation the role of mixtures, since regulatory levels are established only for the isolated agent, however, here it was observed that at permissive levels, the BTEX mixture generated long-term and irreversible effects. |
publishDate |
2023 |
dc.date.accessioned.fl_str_mv |
2023-12-04T19:48:47Z |
dc.date.available.fl_str_mv |
2023-12-04T19:48:47Z |
dc.date.issued.fl_str_mv |
2023-10-30 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
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http://repositorio.ufsm.br/handle/1/30790 |
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http://repositorio.ufsm.br/handle/1/30790 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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200800000002 |
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600 600 600 600 600 600 600 600 |
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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 Santa Maria Centro de Ciências Naturais e Exatas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.publisher.initials.fl_str_mv |
UFSM |
dc.publisher.country.fl_str_mv |
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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