Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides
Ano de defesa: | 2010 |
---|---|
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
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica
|
Departamento: |
Bioquímica
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/4419 |
Resumo: | Methylmercury (MeHg) is an important environmental toxicant that may cause irreversible neurobehavioral and neuropsychological disorders in humans and experimental animals. The major mechanisms of MeHg-induced toxicity currently being explored are the disruption of intracellular calcium homeostasis, the induction of oxidative stress, inhibition of neuronal Na+/K+ -ATPase activity and change the status of antioxidant systems. In addition, recent data reported the involvement of MeHg toxicity with damage in thioredoxin system. On the other hand, flavonoids have been reported to possess divalent metal chelating properties, antioxidant activities and to readily permeate the blood brain barrier. They can also provide neuroprotection in a wide array of cellular and animal models of neurological diseases, including protection against MeHg toxicity. However, the exact mechanism of MeHg toxicity remain unclear and limited data on the interaction of MeHg with flavonoids are avaliable in literature. In view of this, our study evaluated the mechanisms of MeHg toxicity in vivo and in vitro models and evaluated the performance of different flavonoids: quercetin, quercitrin and rutin in diferent models of MeHg toxicity. Our study showed that MeHg (100 μM) caused lipid peroxidation and reactive oxygen species (ROS) generation in brain cortical slices. Quercitrin and quercetin protected against this toxicity and mitochondria from MeHg (5 μM)-induced ROS generation. In contrast, rutin did not afford a significant protective effect against MeHg (100 μM)-induced lipid peroxidation and ROS production in cortical brain slices. MeHg-generated ROS in cortical slices was dependent upon an increase in intracellular calcium levels. In vivo studies with mice treated during 30 days with MeHg (5mg/Kg) orally, presented a marked increase in toxicity parameters (loss in body weight gain, increased in micronucleis frequencies, nefrotoxicity), decrease in motor system performance (locomotor activity and motor coordination) and spatial memory deficiency as well as alteration in some biochemical parameters (decrease in glutathione peroxidase and Na+/K+ ATPase activity, increase in lipid peroxidation). The co-treatment with quercitrin (10mg/kg) intraperitoneally, decreased the behavior alterations manly by decreased lipid peroxidation levels, maintained the Na+/K+ ATPase and GPx activities. In addition, our study demonstrated, for the first time, that MeHg inhibited the activity of thioredoxin reductase. A single oral MeHg administration (1, 5 and 10 mg/Kg) caused a marked inhibition of kidney TrxR, while in liver a significant inhibition was observed after exposure to 5 and 10 mg/Kg of MeHg (TrxR was determined 24 hours after MeHg). In brain, MeHg did not inhibit TrxR. In vitro results demonstrated that MeHg inhibited brain (0.05 1 μM) , liver (0.05 1 μM) and kidney (0.025 1 μM) TrxR in a dose dependent manner Here, we have extended the characterization of mechanisms associated with the neuroprotective effects of flavonoids quercetin and quercitrin against MeHg-induced toxicity. In addition, we provided novel data establishing that (1) calcium plays a central role in MeHg toxicity, (2) in brain slices MeHg induces mitochondrial oxidative stress both via direct interaction with mitochondria as well as via mitochondria- indirect mechanisms. In addition (3) MeHg (5mg/kg) caused a number of behavioural alterations that are related with an inhibition of cerebelar and cerebral GPx and Na+/K+ ATPase activities and (4) increased in lipid peroxidation.The higly affinity of MeHg to selenol groups of endogenous molecules can lead to (5) inhibition of thioredoxin reductase that can contribute to MeHg toxicity. We conclude that MeHg lead to increase in mitochondria ROS generation that contributes to increase in lipid peroxidation. In addition, the inhibition of important antioxidant enzymes such as GPx ans TrxR can contribute to oxidative damage that can be related to development of behavioral damage. In this view the antioxidant activity of flavonoids quercetin and quercitrin seems to be direct associate with the capacity of flavonoids to confere protection against MeHg toxicity. |
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2017-04-202017-04-202010-08-12WAGNER, Caroline. Mechanisms of methilmercury toxicity: protective effect of flavonoids. 2010. 146 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2010.http://repositorio.ufsm.br/handle/1/4419Methylmercury (MeHg) is an important environmental toxicant that may cause irreversible neurobehavioral and neuropsychological disorders in humans and experimental animals. The major mechanisms of MeHg-induced toxicity currently being explored are the disruption of intracellular calcium homeostasis, the induction of oxidative stress, inhibition of neuronal Na+/K+ -ATPase activity and change the status of antioxidant systems. In addition, recent data reported the involvement of MeHg toxicity with damage in thioredoxin system. On the other hand, flavonoids have been reported to possess divalent metal chelating properties, antioxidant activities and to readily permeate the blood brain barrier. They can also provide neuroprotection in a wide array of cellular and animal models of neurological diseases, including protection against MeHg toxicity. However, the exact mechanism of MeHg toxicity remain unclear and limited data on the interaction of MeHg with flavonoids are avaliable in literature. In view of this, our study evaluated the mechanisms of MeHg toxicity in vivo and in vitro models and evaluated the performance of different flavonoids: quercetin, quercitrin and rutin in diferent models of MeHg toxicity. Our study showed that MeHg (100 μM) caused lipid peroxidation and reactive oxygen species (ROS) generation in brain cortical slices. Quercitrin and quercetin protected against this toxicity and mitochondria from MeHg (5 μM)-induced ROS generation. In contrast, rutin did not afford a significant protective effect against MeHg (100 μM)-induced lipid peroxidation and ROS production in cortical brain slices. MeHg-generated ROS in cortical slices was dependent upon an increase in intracellular calcium levels. In vivo studies with mice treated during 30 days with MeHg (5mg/Kg) orally, presented a marked increase in toxicity parameters (loss in body weight gain, increased in micronucleis frequencies, nefrotoxicity), decrease in motor system performance (locomotor activity and motor coordination) and spatial memory deficiency as well as alteration in some biochemical parameters (decrease in glutathione peroxidase and Na+/K+ ATPase activity, increase in lipid peroxidation). The co-treatment with quercitrin (10mg/kg) intraperitoneally, decreased the behavior alterations manly by decreased lipid peroxidation levels, maintained the Na+/K+ ATPase and GPx activities. In addition, our study demonstrated, for the first time, that MeHg inhibited the activity of thioredoxin reductase. A single oral MeHg administration (1, 5 and 10 mg/Kg) caused a marked inhibition of kidney TrxR, while in liver a significant inhibition was observed after exposure to 5 and 10 mg/Kg of MeHg (TrxR was determined 24 hours after MeHg). In brain, MeHg did not inhibit TrxR. In vitro results demonstrated that MeHg inhibited brain (0.05 1 μM) , liver (0.05 1 μM) and kidney (0.025 1 μM) TrxR in a dose dependent manner Here, we have extended the characterization of mechanisms associated with the neuroprotective effects of flavonoids quercetin and quercitrin against MeHg-induced toxicity. In addition, we provided novel data establishing that (1) calcium plays a central role in MeHg toxicity, (2) in brain slices MeHg induces mitochondrial oxidative stress both via direct interaction with mitochondria as well as via mitochondria- indirect mechanisms. In addition (3) MeHg (5mg/kg) caused a number of behavioural alterations that are related with an inhibition of cerebelar and cerebral GPx and Na+/K+ ATPase activities and (4) increased in lipid peroxidation.The higly affinity of MeHg to selenol groups of endogenous molecules can lead to (5) inhibition of thioredoxin reductase that can contribute to MeHg toxicity. We conclude that MeHg lead to increase in mitochondria ROS generation that contributes to increase in lipid peroxidation. In addition, the inhibition of important antioxidant enzymes such as GPx ans TrxR can contribute to oxidative damage that can be related to development of behavioral damage. In this view the antioxidant activity of flavonoids quercetin and quercitrin seems to be direct associate with the capacity of flavonoids to confere protection against MeHg toxicity.O metilmercúrio (MeHg) é um importante agente tóxico ambiental que pode causar desordens neurocomportamentais e neurofisiológicas irreversíveis em humanos e animais experimentais. Os principais mecanismos pelos quais o MeHg induz toxicidade são: a ruptura na homeostase do cálcio intracelular, a indução de estresse oxidativo, a inibição da atividade da Na+/K+ ATPase neuronal e mudanças nos níveis das enzimas antioxidantes. Adicionalmente, dados recentes relatam o envolvimento do sistema da tiorredoxina como um dos alvos de toxicidade do MeHg. Por outro lado, os flavonóides possuem propriedades quelantes para metal divalente, atividade antioxidante e são permeáveis a barreira cérebro-sangue. Além disso, eles podem oferecer neuroproteção a uma variedade de modelos animais e celulares de doenças neurológicas, incluindo proteção contra a toxicidade do MeHg. Considerando que o exato mecanismo pelo qual o MeHg exerce toxicidade permanece desconhecido e que poucos e controversos dados sobre a interação do MeHg com flavonóides são encontrados na literatura, este estudo avaliou os mecanismos de toxicidade do MeHg em modelos in vitro e in vivo bem como, o desempenho de diferentes flavonóides: quercetina, quercitrina e rutina em diferentes modelos de toxicidade induzidos pelo MeHg. Nosso estudo mostrou que o MeHg (100μM) causou aumento na peroxidação lipídica e na produção de espécies reativas de oxigênio (EROs) em fatias de córtex de ratos. Os flavonóides quercitrina (25 μg/mL) e quercetina (5, 10 e 25 μg/mL) protegeram contra esta toxicidade, e contra o aumento de ERO produzidas pelo MeHg (5μM) nas mitocôndrias. Diferentemente, o flavonóide rutina não obteve efeito protetor contra a indução da peroxidação lipídica e produção de ERO induzidas pelo MeHg em fatias corticais de cérebro. O aumento na produção de ERO, geradas pelo MeHg, foi dependente do aumento dos níveis intracelulares de cálcio (artigo 1). Já, estudos in vivo com camundongos tratados oralmente com MeHg (5mg/kg), durante 30 dias, mostraram um marcado aumento nos parâmetros de toxicidade (diminuição no ganho de peso, aumento na freqüência de micronúcleos e nefrotoxicidade), diminuição no desempenho do sistema motor (atividade locomotora e coordenação motora), e deficiência na memória espacial, bem como alterações em vários parâmetros bioquímicos (diminuição na atividade da glutationa peroxidase (GPx) e Na+/K+ ATPase e aumento na peroxidação lipídica). O co-tratamento com quercitrina (10mg/kg) pela via intraperitoneal, diminuiu as alterações comportamentais principalmente por diminuir os níveis de peroxidação lipídica e manter a atividade da GPx e da Na+/K+ ATPase iguais aos níveis do controle (manuscrito 1). Além disso, nosso estudo demonstrou, pela primeira vez, que o MeHg inibe a atividade da tiorredoxina redutase (TrxR). Uma única administração oral de MeHg (1, 5, 10 mg/kg), causou uma marcada inibição na atividade da TrxR renal, enquanto no fígad observou-se uma inibição significativa após exposição a 5 e 10 mg/kg (a atividade da TrxR foi determinada 24 horas após a administração de MeHg). No cérebro, o MeHg não inibiu a atividade da TrxR in vivo (artigo 2). Já os resultados in vitro revelaram que o MeHg causou uma inibição concentração dependente na atividade da enzima TrxR isolada de cérebro (0,05 1 μM) fígado (0,05 - 1 μM) e rim (0,025 1 μM). Assim, nós ampliamos a caracterização dos mecanismos associados com os efeitos neuroprotetores dos flavonóides quercetina e quercitrina na toxicidade induzida pelo MeHg. Adicionalmente, outros dados sobre a toxicidade do MeHg, foram obtidos, tais como: (1) o cálcio desempenha um papel central na toxicidade do MeHg, (2) em fatias de cérebro de ratos o MeHg induz estresse oxidativo mitocondrial via interação direta com as mitocôndrias, bem como via mecanismos mitocondriais indiretos. Além disso, (3) o MeHg (5mg/kg) pode levar a inúmeras alterações comportamentais que podem estar relacionadas à inibição da atividade das enzimas GPx e Na+/K+ ATPase e (4) aumento na peroxidação lipídica. A alta afinidade do MeHg por grupos selenóis das moléculas endógenas pode levar (5) a inibição da TrxR o que pode contribuir para a toxicidade do MeHg. Podemos concluir que o MeHg leva a um aumento na produção de ERO pelas mitocôndrias, o que contribui para um aumento na peroxidação lipídica induzida pelo MeHg. Além disso, a inibição de importantes enzimas antioxidantes como a GPx e a TrxR podem contribuir para aumentar o dano oxidativo, que parece estar relacionado com o aparecimento dedanos comportamentais. Desta forma a atividade antioxidante dos flavonóides quercetina e quercitrina parece estar diretamente associada à capacidade destes compostos emproteger contra a toxicidade do MeHg.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaMeHgFlavonóidesEstresse oxidativoTiorredoxina redutaseAntioxidantesCálcioMeHgFlavonoidsOxidative stressThioredoxin redutaseAntioxidantCalciumCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEstudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóidesMechanisms of methilmercury toxicity: protective effect of flavonoidsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisRocha, João Batista Teixeira dahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782281H2Nogueira, Cristina Waynehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9Gonçalves, Carlos Alberto Saraivahttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785436Y4Brandão, Ricardohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779496T3Franco, Jeferson Luishttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705814T8Burger, Marilise Escobarhttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4745160D1Wagner, Caroline20080000000240050030030030030030030027186f63-94dd-4f0f-8181-7ce1b083500960f77f4f-a19a-4cbd-998d-8b01221bd621c2b1a64f-5f22-4779-9732-0c543f42b42dc5c8d89a-5cff-43c3-9c54-6e54a7311c41e6617091-34a2-401c-87dc-5d8877667a001133a5ad-51c6-405e-b37c-56e2810aafb6fef98c94-2404-4764-a10c-561dd9b55f47info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALWAGNER, CAROLINA.pdfapplication/pdf4648775http://repositorio.ufsm.br/bitstream/1/4419/1/WAGNER%2c%20CAROLINA.pdf641adc5bcc13297fa122cb2f3cdc19ccMD51TEXTWAGNER, CAROLINA.pdf.txtWAGNER, CAROLINA.pdf.txtExtracted texttext/plain192277http://repositorio.ufsm.br/bitstream/1/4419/2/WAGNER%2c%20CAROLINA.pdf.txt825fb9d22ce5aa4e9b5b4e023d70fb48MD52THUMBNAILWAGNER, CAROLINA.pdf.jpgWAGNER, CAROLINA.pdf.jpgIM Thumbnailimage/jpeg6171http://repositorio.ufsm.br/bitstream/1/4419/3/WAGNER%2c%20CAROLINA.pdf.jpgd442c441cc3e3584acd7cdfb4841e5e1MD531/44192017-07-25 11:06:37.735oai:repositorio.ufsm.br:1/4419Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-07-25T14:06:37Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides |
dc.title.alternative.eng.fl_str_mv |
Mechanisms of methilmercury toxicity: protective effect of flavonoids |
title |
Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides |
spellingShingle |
Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides Wagner, Caroline MeHg Flavonóides Estresse oxidativo Tiorredoxina redutase Antioxidantes Cálcio MeHg Flavonoids Oxidative stress Thioredoxin redutase Antioxidant Calcium CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides |
title_full |
Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides |
title_fullStr |
Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides |
title_full_unstemmed |
Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides |
title_sort |
Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides |
author |
Wagner, Caroline |
author_facet |
Wagner, Caroline |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Rocha, João Batista Teixeira da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4782281H2 |
dc.contributor.advisor-co1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4728219Y9 |
dc.contributor.referee1.fl_str_mv |
Gonçalves, Carlos Alberto Saraiva |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785436Y4 |
dc.contributor.referee2.fl_str_mv |
Brandão, Ricardo |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4779496T3 |
dc.contributor.referee3.fl_str_mv |
Franco, Jeferson Luis |
dc.contributor.referee3Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4705814T8 |
dc.contributor.referee4.fl_str_mv |
Burger, Marilise Escobar |
dc.contributor.referee4Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4709238P6 |
dc.contributor.authorLattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4745160D1 |
dc.contributor.author.fl_str_mv |
Wagner, Caroline |
contributor_str_mv |
Rocha, João Batista Teixeira da Nogueira, Cristina Wayne Gonçalves, Carlos Alberto Saraiva Brandão, Ricardo Franco, Jeferson Luis Burger, Marilise Escobar |
dc.subject.por.fl_str_mv |
MeHg Flavonóides Estresse oxidativo Tiorredoxina redutase Antioxidantes Cálcio |
topic |
MeHg Flavonóides Estresse oxidativo Tiorredoxina redutase Antioxidantes Cálcio MeHg Flavonoids Oxidative stress Thioredoxin redutase Antioxidant Calcium CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
MeHg Flavonoids Oxidative stress Thioredoxin redutase Antioxidant Calcium |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Methylmercury (MeHg) is an important environmental toxicant that may cause irreversible neurobehavioral and neuropsychological disorders in humans and experimental animals. The major mechanisms of MeHg-induced toxicity currently being explored are the disruption of intracellular calcium homeostasis, the induction of oxidative stress, inhibition of neuronal Na+/K+ -ATPase activity and change the status of antioxidant systems. In addition, recent data reported the involvement of MeHg toxicity with damage in thioredoxin system. On the other hand, flavonoids have been reported to possess divalent metal chelating properties, antioxidant activities and to readily permeate the blood brain barrier. They can also provide neuroprotection in a wide array of cellular and animal models of neurological diseases, including protection against MeHg toxicity. However, the exact mechanism of MeHg toxicity remain unclear and limited data on the interaction of MeHg with flavonoids are avaliable in literature. In view of this, our study evaluated the mechanisms of MeHg toxicity in vivo and in vitro models and evaluated the performance of different flavonoids: quercetin, quercitrin and rutin in diferent models of MeHg toxicity. Our study showed that MeHg (100 μM) caused lipid peroxidation and reactive oxygen species (ROS) generation in brain cortical slices. Quercitrin and quercetin protected against this toxicity and mitochondria from MeHg (5 μM)-induced ROS generation. In contrast, rutin did not afford a significant protective effect against MeHg (100 μM)-induced lipid peroxidation and ROS production in cortical brain slices. MeHg-generated ROS in cortical slices was dependent upon an increase in intracellular calcium levels. In vivo studies with mice treated during 30 days with MeHg (5mg/Kg) orally, presented a marked increase in toxicity parameters (loss in body weight gain, increased in micronucleis frequencies, nefrotoxicity), decrease in motor system performance (locomotor activity and motor coordination) and spatial memory deficiency as well as alteration in some biochemical parameters (decrease in glutathione peroxidase and Na+/K+ ATPase activity, increase in lipid peroxidation). The co-treatment with quercitrin (10mg/kg) intraperitoneally, decreased the behavior alterations manly by decreased lipid peroxidation levels, maintained the Na+/K+ ATPase and GPx activities. In addition, our study demonstrated, for the first time, that MeHg inhibited the activity of thioredoxin reductase. A single oral MeHg administration (1, 5 and 10 mg/Kg) caused a marked inhibition of kidney TrxR, while in liver a significant inhibition was observed after exposure to 5 and 10 mg/Kg of MeHg (TrxR was determined 24 hours after MeHg). In brain, MeHg did not inhibit TrxR. In vitro results demonstrated that MeHg inhibited brain (0.05 1 μM) , liver (0.05 1 μM) and kidney (0.025 1 μM) TrxR in a dose dependent manner Here, we have extended the characterization of mechanisms associated with the neuroprotective effects of flavonoids quercetin and quercitrin against MeHg-induced toxicity. In addition, we provided novel data establishing that (1) calcium plays a central role in MeHg toxicity, (2) in brain slices MeHg induces mitochondrial oxidative stress both via direct interaction with mitochondria as well as via mitochondria- indirect mechanisms. In addition (3) MeHg (5mg/kg) caused a number of behavioural alterations that are related with an inhibition of cerebelar and cerebral GPx and Na+/K+ ATPase activities and (4) increased in lipid peroxidation.The higly affinity of MeHg to selenol groups of endogenous molecules can lead to (5) inhibition of thioredoxin reductase that can contribute to MeHg toxicity. We conclude that MeHg lead to increase in mitochondria ROS generation that contributes to increase in lipid peroxidation. In addition, the inhibition of important antioxidant enzymes such as GPx ans TrxR can contribute to oxidative damage that can be related to development of behavioral damage. In this view the antioxidant activity of flavonoids quercetin and quercitrin seems to be direct associate with the capacity of flavonoids to confere protection against MeHg toxicity. |
publishDate |
2010 |
dc.date.issued.fl_str_mv |
2010-08-12 |
dc.date.accessioned.fl_str_mv |
2017-04-20 |
dc.date.available.fl_str_mv |
2017-04-20 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
WAGNER, Caroline. Mechanisms of methilmercury toxicity: protective effect of flavonoids. 2010. 146 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2010. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/4419 |
identifier_str_mv |
WAGNER, Caroline. Mechanisms of methilmercury toxicity: protective effect of flavonoids. 2010. 146 f. Tese (Doutorado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2010. |
url |
http://repositorio.ufsm.br/handle/1/4419 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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200800000002 |
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Universidade Federal de Santa Maria |
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Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
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UFSM |
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BR |
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Bioquímica |
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Universidade Federal de Santa Maria |
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Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
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