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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Mecanismos 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 cerevisiaeMetilmercúrioDisseleneto de difenilaSaccharomyces cerevisiaeEstresse oxidativoDefesas antioxidantesMethylmercuryDiphenyl diselenideOxidative stressAntioxidant defensesCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAHumans 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.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESOs 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.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasDalla 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/3179264934205423Lovato, Fabricio Luís2019-07-09T22:32:16Z2019-07-09T22:32:16Z2015-12-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/17374porAttribution-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:UFSM2019-07-10T06:00:34Zoai:repositorio.ufsm.br:1/17374Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-07-10T06:00:34Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Mecanismos envolvidos na proteção do disseleneto de difenila sobre a toxicidade induzida por metilmercúrio em Saccharomyces cerevisiae 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.none.fl_str_mv |
Dalla Corte, Cristiane Lenz http://lattes.cnpq.br/5296284169605317 Rocha, Joao Batista Teixeira da http://lattes.cnpq.br/3935055744673018 Rosemberg, Denis Broock http://lattes.cnpq.br/7713953979203056 Saffi, Jenifer http://lattes.cnpq.br/3179264934205423 |
dc.contributor.author.fl_str_mv |
Lovato, Fabricio Luís |
dc.subject.por.fl_str_mv |
Metilmercúrio Disseleneto de difenila Saccharomyces cerevisiae Estresse oxidativo Defesas antioxidantes Methylmercury Diphenyl diselenide Oxidative stress Antioxidant defenses CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Metilmercúrio Disseleneto de difenila Saccharomyces cerevisiae Estresse oxidativo Defesas antioxidantes Methylmercury Diphenyl diselenide Oxidative stress Antioxidant defenses 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.none.fl_str_mv |
2015-12-14 2019-07-09T22:32:16Z 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 |
format |
masterThesis |
status_str |
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 |
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 |
_version_ |
1805922044673523712 |