Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/17374 |
Resumo: | Humans are usually exposed to organic form of mercury, the organometallic cation methylmercury ([CH3Hg]+, MeHg), by eating fish and seafood. The neurotoxic effects of MeHg are already widely known. Individuals exposed to high concentrations of this compound showed sensory disorders in the hands and feet, hearing and visual impairment, weakness and, in extreme cases, paralysis and death. Although the exact mechanisms underlying the toxicity of MeHg are not yet completely understood, there is evidence that oxidative stress plays a central role. The organic compound derived from selenium, diphenyl diselenide [(PhSe)2] is a simple electrophilic synthetic intermediate in the synthesis of various organic compounds of pharmaceutical interest containing selenium and have already presented antioxidant, anti-nociceptive, anti-inflammatory, antihyperglycemic, antiteratogenic, among others properties. The aim of this study was to investigate some mechanisms involved in the protective effect of (PhSe)2 on the toxicity induced by MeHg, using wild and knockout strains of S. cerevisiae for different enzymes and proteins linked to the antioxidant defense system. Using these strains, as well as different concentrations (PhSe)2 and/or MeHg, the specific objectives of this study were: i) to evaluate the growth inhibition; ii) to quantify the production of reactive oxygen species; iii) to evaluate the permeability of cell membranes; iv) to quantify the intracellular GSH content. This study sheds light on the mechanisms involved in the protection of diphenyl diselenide against MeHg indicating the involvement of the antioxidant defense system of S. cerevisiae and the sequestering of Hg in (PhSe)2 protection. The compound diphenyl diselenide protects against the toxicity induced by methylmercury, as noted in the recovery of growth and lower levels of reactive oxygen species, membrane permeability and restoration of intracellular GSH content in yeasts treated with both compounds. The protective effect triggered by diphenyl diselenide seems to be related with the activation of some enzymes of antioxidant system of yeasts. Not all analyzed antioxidant enzymes had the same participation or importance in the protection mechanism. Functional and genetic similarities between yeast and mammalian cells suggests that the elucidation of these mechanisms will help direct the search to human. |
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2019-07-09T22:32:16Z2019-07-09T22:32:16Z2015-12-14http://repositorio.ufsm.br/handle/1/17374Humans are usually exposed to organic form of mercury, the organometallic cation methylmercury ([CH3Hg]+, MeHg), by eating fish and seafood. The neurotoxic effects of MeHg are already widely known. Individuals exposed to high concentrations of this compound showed sensory disorders in the hands and feet, hearing and visual impairment, weakness and, in extreme cases, paralysis and death. Although the exact mechanisms underlying the toxicity of MeHg are not yet completely understood, there is evidence that oxidative stress plays a central role. The organic compound derived from selenium, diphenyl diselenide [(PhSe)2] is a simple electrophilic synthetic intermediate in the synthesis of various organic compounds of pharmaceutical interest containing selenium and have already presented antioxidant, anti-nociceptive, anti-inflammatory, antihyperglycemic, antiteratogenic, among others properties. The aim of this study was to investigate some mechanisms involved in the protective effect of (PhSe)2 on the toxicity induced by MeHg, using wild and knockout strains of S. cerevisiae for different enzymes and proteins linked to the antioxidant defense system. Using these strains, as well as different concentrations (PhSe)2 and/or MeHg, the specific objectives of this study were: i) to evaluate the growth inhibition; ii) to quantify the production of reactive oxygen species; iii) to evaluate the permeability of cell membranes; iv) to quantify the intracellular GSH content. This study sheds light on the mechanisms involved in the protection of diphenyl diselenide against MeHg indicating the involvement of the antioxidant defense system of S. cerevisiae and the sequestering of Hg in (PhSe)2 protection. The compound diphenyl diselenide protects against the toxicity induced by methylmercury, as noted in the recovery of growth and lower levels of reactive oxygen species, membrane permeability and restoration of intracellular GSH content in yeasts treated with both compounds. The protective effect triggered by diphenyl diselenide seems to be related with the activation of some enzymes of antioxidant system of yeasts. Not all analyzed antioxidant enzymes had the same participation or importance in the protection mechanism. Functional and genetic similarities between yeast and mammalian cells suggests that the elucidation of these mechanisms will help direct the search to human.Os seres humanos normalmente são expostos à forma orgânica do Hg, o cátion organometálico metilmercúrio ([CH3Hg]+, MeHg), através da alimentação com peixes e frutos do mar. Os efeitos neurotóxicos do MeHg já são amplamente conhecidos. Indivíduos expostos a altas concentrações desse composto apresentaram distúrbios sensoriais nas mãos e pés, disfunção auditiva e visual, fraqueza e, em casos extremos, paralisia e morte. Embora os mecanismos exatos subjacentes à toxicidade do MeHg ainda não estejam totalmente elucidados, há evidências de que o estresse oxidativo desempenha um papel central nesse processo. O composto orgânico derivado do selênio, disseleneto de difenila [(PhSe)2] é um intermediário sintético eletrofílico simples na síntese de vários compostos orgânicos de interesse farmacológico contendo selênio, tendo apresentado as propriedades antioxidante, anti-nociceptiva, anti-inflamatória, antihiperglicêmica, antiteratogênica, entre outras. O objetivo principal deste trabalho foi investigar alguns mecanismos envolvidas no efeito protetor do (PhSe)2 sobre a toxicidade induzida por MeHg, utilizando cepas selvagem e knockout de Saccharomyces cerevisiae para diferentes enzimas e proteínas ligadas ao sistema de defesa antioxidante. Utilizando-se dessas linhagens, bem como diferentes concentrações de (PhSe)2 e/ou MeHg, os objetivos específicos desse trabalho foram: i) avaliar a inibição do crescimento; ii) quantificar a produção de espécies reativas do oxigênio; iii) avaliar a permeabilidade das membranas celulares; iv) quantificar o conteúdo intracelular de GSH. O presente estudo lança luz sobre os mecanismos envolvidos na proteção do disseleneto de difenila contra o MeHg indicando o envolvimento do sistema de defesa antioxidante de S. cerevisiae e o sequestro de Hg na proteção do (PhSe)2. O composto disseleneto de difenila protege contra a toxicidade induzida pelo metilmercúrio, conforme observou-se na recuperação do crescimento e menores índices de espécies reativas de oxigênio, permeabilidade de membrana e restauração do conteúdo intracelular de GSH, em leveduras tratadas com ambos os compostos. O efeito protetor desencadeado pelo disseleneto de difenila parece estar relacionado com a ativação de algumas enzimas do sistema antioxidante das leveduras. Nem todas as enzimas antioxidantes analisadas tiveram a mesma participação ou importância no mecanismo de proteção. A similaridade funcional e genética entre células de leveduras e de mamíferos sugere que a elucidação desses mecanismos ajudará a direcionar a pesquisa para humanos.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/openAccessMetilmercúrioDisseleneto de difenilaSaccharomyces cerevisiaeEstresse oxidativoDefesas antioxidantesMethylmercuryDiphenyl diselenideOxidative stressAntioxidant defensesCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAMecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiaeMechanisms involved in the action of diphenyl diselenide on methylmercury-induced toxicity in Saccharomyces cerevisiaeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisDalla Corte, Cristiane Lenzhttp://lattes.cnpq.br/5296284169605317Rocha, Joao Batista Teixeira dahttp://lattes.cnpq.br/3935055744673018Rosemberg, Denis Broockhttp://lattes.cnpq.br/7713953979203056Saffi, Jeniferhttp://lattes.cnpq.br/3179264934205423http://lattes.cnpq.br/8943577436722902Lovato, Fabricio Luís2008000000026004297bf04-ccc8-4d7a-b4f2-53aa4223e191ce0894bf-1722-492b-bba9-ad171c1ca18214d04cad-6929-4697-a8d6-d1303391d218c677f64b-5cc5-4b69-a688-583d9209b1b009e1f5b1-b64d-4fc7-b98c-c06fca85fc28reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGBT_2015_LOVATO_FABRICIO.pdfDIS_PPGBT_2015_LOVATO_FABRICIO.pdfDissertação de Mestradoapplication/pdf3864674http://repositorio.ufsm.br/bitstream/1/17374/1/DIS_PPGBT_2015_LOVATO_FABRICIO.pdffc3ca7c361f72df99c8dd815db2bc1c6MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae |
dc.title.alternative.eng.fl_str_mv |
Mechanisms involved in the action of diphenyl diselenide on methylmercury-induced toxicity in Saccharomyces cerevisiae |
title |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae |
spellingShingle |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae Lovato, Fabricio Luís Metilmercúrio Disseleneto de difenila Saccharomyces cerevisiae Estresse oxidativo Defesas antioxidantes Methylmercury Diphenyl diselenide Oxidative stress Antioxidant defenses CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae |
title_full |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae |
title_fullStr |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae |
title_full_unstemmed |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae |
title_sort |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae |
author |
Lovato, Fabricio Luís |
author_facet |
Lovato, Fabricio Luís |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Dalla Corte, Cristiane Lenz |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5296284169605317 |
dc.contributor.advisor-co1.fl_str_mv |
Rocha, Joao Batista Teixeira da |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/3935055744673018 |
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 |
Saffi, Jenifer |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/3179264934205423 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8943577436722902 |
dc.contributor.author.fl_str_mv |
Lovato, Fabricio Luís |
contributor_str_mv |
Dalla Corte, Cristiane Lenz Rocha, Joao Batista Teixeira da Rosemberg, Denis Broock Saffi, Jenifer |
dc.subject.por.fl_str_mv |
Metilmercúrio Disseleneto de difenila Saccharomyces cerevisiae Estresse oxidativo Defesas antioxidantes Methylmercury Diphenyl diselenide |
topic |
Metilmercúrio Disseleneto de difenila Saccharomyces cerevisiae Estresse oxidativo Defesas antioxidantes Methylmercury Diphenyl diselenide Oxidative stress Antioxidant defenses CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Oxidative stress Antioxidant defenses |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Humans are usually exposed to organic form of mercury, the organometallic cation methylmercury ([CH3Hg]+, MeHg), by eating fish and seafood. The neurotoxic effects of MeHg are already widely known. Individuals exposed to high concentrations of this compound showed sensory disorders in the hands and feet, hearing and visual impairment, weakness and, in extreme cases, paralysis and death. Although the exact mechanisms underlying the toxicity of MeHg are not yet completely understood, there is evidence that oxidative stress plays a central role. The organic compound derived from selenium, diphenyl diselenide [(PhSe)2] is a simple electrophilic synthetic intermediate in the synthesis of various organic compounds of pharmaceutical interest containing selenium and have already presented antioxidant, anti-nociceptive, anti-inflammatory, antihyperglycemic, antiteratogenic, among others properties. The aim of this study was to investigate some mechanisms involved in the protective effect of (PhSe)2 on the toxicity induced by MeHg, using wild and knockout strains of S. cerevisiae for different enzymes and proteins linked to the antioxidant defense system. Using these strains, as well as different concentrations (PhSe)2 and/or MeHg, the specific objectives of this study were: i) to evaluate the growth inhibition; ii) to quantify the production of reactive oxygen species; iii) to evaluate the permeability of cell membranes; iv) to quantify the intracellular GSH content. This study sheds light on the mechanisms involved in the protection of diphenyl diselenide against MeHg indicating the involvement of the antioxidant defense system of S. cerevisiae and the sequestering of Hg in (PhSe)2 protection. The compound diphenyl diselenide protects against the toxicity induced by methylmercury, as noted in the recovery of growth and lower levels of reactive oxygen species, membrane permeability and restoration of intracellular GSH content in yeasts treated with both compounds. The protective effect triggered by diphenyl diselenide seems to be related with the activation of some enzymes of antioxidant system of yeasts. Not all analyzed antioxidant enzymes had the same participation or importance in the protection mechanism. Functional and genetic similarities between yeast and mammalian cells suggests that the elucidation of these mechanisms will help direct the search to human. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-12-14 |
dc.date.accessioned.fl_str_mv |
2019-07-09T22:32:16Z |
dc.date.available.fl_str_mv |
2019-07-09T22:32:16Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/17374 |
url |
http://repositorio.ufsm.br/handle/1/17374 |
dc.language.iso.fl_str_mv |
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 |
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 |
dc.source.none.fl_str_mv |
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