Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais
Ano de defesa: | 2018 |
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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
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Departamento: |
Bioquímica
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País: |
Brasil
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Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/16714 |
Resumo: | The transition metals iron (Fe2+) and copper (Cu2+) are vital trace elements due to oxi-reducing properties. However, the free Fe2+ and Cu2+ accumulation can lead to oxidative stress (OS), by catalisis the Fenton reaction. The OS can lead to damage in biological macromolecules and is involved in the etiology of various pathologies, especially in liver and central nervous system (CNS), where Fe2+ and Cu2+ accumulates. Therefore, there is a growing interest for agents able to minimize or block the toxic effects of Fe2+and Cu2+. The Peumus boldus extract, used for the treatment of liver disorders, has shown antioxidant properties in different in vivo and in vitro experimental models, as well as boldine, the main alkaloid isolated from the plant. However, the pharmacological properties of P. boldus against Fe2+- induced hepatotoxicity, and Cu2+-induced toxicity, remains unexplored. Likewise, there is no data on the possible beneficial effects of P. boldus on the Cu2+ toxicity using Drosophila melanogaster as an experimental model, a specie widely used due to the fact of sharing well conserved genes with mammals such as those related to Cu2+ homeostasis. Thus, the main objective of this study was to evaluate the possible protective effect of P. boldus and boldine against Fe2+-induced hepatic oxidative damage in vitro using rat liver mitochondria, and the effect of P. boldus supplementation on molecular alterations induced by exposure to Cu2+ in D. melanogaster, in vivo and ex vivo. The results show that P.boldus aqueous extract was more efficient than boldine in decreasing the lipid peroxidation, the reactive oxygen species (ROS) production, and swelling induced by Fe2+ in hepatic mitochondria of rats. The antioxidant activity assays in non-biological systems showed that P. boldus was effective in chelating Fe2+, whereas boldine presented higher reducing power than P. boldus. Cu2+ impaired in the negative geotaxis performance (i.e. motor climbing capability), but P. boldus co-exposure was effective to protect against the Cu2+-induced toxicity. Acetylcholinesterase (AChE) and glutathione S-transferase (GST) activity decreased significantly in D. melanogaster after Cu2+ exposure. P. boldus co-treatment restored enzyme activities to control levels. In addition, Cu2+ exposure increased the mRNA levels of the enzymes, superoxide dismutase (Sod1), catalase (Cat), thioredoxin reductase (TrxR1), nuclear factor erythroid 2– related factor 2 (Nrf2), acetylcholinesterase (Ace) and Cu2+ transporters, P-type ATPase (Atp7A) and copper uptake protein 1 (Ctr1A). These alterations were restored to control levels by co-treatment with P.boldus. These findings suggest that P. boldus could be considered a promising plant in modulation of toxicity induced by an excess of Fe2+ and Cu2+. P.boldus and boldine can have antioxidant properties in protection against hepatic diseases associated with Fe-free and OS. In summary, these results contribute to the advancement of the investigations of agents that may in the assist therapy of intoxications or autosomal diseases linked to an excess of Fe2+ and Cu2+. |
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2019-05-31T16:14:33Z2019-05-31T16:14:33Z2018-08-10http://repositorio.ufsm.br/handle/1/16714The transition metals iron (Fe2+) and copper (Cu2+) are vital trace elements due to oxi-reducing properties. However, the free Fe2+ and Cu2+ accumulation can lead to oxidative stress (OS), by catalisis the Fenton reaction. The OS can lead to damage in biological macromolecules and is involved in the etiology of various pathologies, especially in liver and central nervous system (CNS), where Fe2+ and Cu2+ accumulates. Therefore, there is a growing interest for agents able to minimize or block the toxic effects of Fe2+and Cu2+. The Peumus boldus extract, used for the treatment of liver disorders, has shown antioxidant properties in different in vivo and in vitro experimental models, as well as boldine, the main alkaloid isolated from the plant. However, the pharmacological properties of P. boldus against Fe2+- induced hepatotoxicity, and Cu2+-induced toxicity, remains unexplored. Likewise, there is no data on the possible beneficial effects of P. boldus on the Cu2+ toxicity using Drosophila melanogaster as an experimental model, a specie widely used due to the fact of sharing well conserved genes with mammals such as those related to Cu2+ homeostasis. Thus, the main objective of this study was to evaluate the possible protective effect of P. boldus and boldine against Fe2+-induced hepatic oxidative damage in vitro using rat liver mitochondria, and the effect of P. boldus supplementation on molecular alterations induced by exposure to Cu2+ in D. melanogaster, in vivo and ex vivo. The results show that P.boldus aqueous extract was more efficient than boldine in decreasing the lipid peroxidation, the reactive oxygen species (ROS) production, and swelling induced by Fe2+ in hepatic mitochondria of rats. The antioxidant activity assays in non-biological systems showed that P. boldus was effective in chelating Fe2+, whereas boldine presented higher reducing power than P. boldus. Cu2+ impaired in the negative geotaxis performance (i.e. motor climbing capability), but P. boldus co-exposure was effective to protect against the Cu2+-induced toxicity. Acetylcholinesterase (AChE) and glutathione S-transferase (GST) activity decreased significantly in D. melanogaster after Cu2+ exposure. P. boldus co-treatment restored enzyme activities to control levels. In addition, Cu2+ exposure increased the mRNA levels of the enzymes, superoxide dismutase (Sod1), catalase (Cat), thioredoxin reductase (TrxR1), nuclear factor erythroid 2– related factor 2 (Nrf2), acetylcholinesterase (Ace) and Cu2+ transporters, P-type ATPase (Atp7A) and copper uptake protein 1 (Ctr1A). These alterations were restored to control levels by co-treatment with P.boldus. These findings suggest that P. boldus could be considered a promising plant in modulation of toxicity induced by an excess of Fe2+ and Cu2+. P.boldus and boldine can have antioxidant properties in protection against hepatic diseases associated with Fe-free and OS. In summary, these results contribute to the advancement of the investigations of agents that may in the assist therapy of intoxications or autosomal diseases linked to an excess of Fe2+ and Cu2+.Os metais de transição ferro (Fe2+) e cobre (Cu2+) são elementos vitais devido as suas propriedades de oxido-redução. Porém, o acúmulo de Fe2+ e Cu2+ na forma livre pode causar estresse oxidativo (EO), por serem catalisadores da reação de Fenton. Esta condição pode levar a danos em macromoléculas biológicas e está envolvida na etiologia de várias patologias, principalmente a nível hepático e neurológico, onde Fe2+ e Cu2+ se acumulam. Logo, existe um interesse crescente na busca de agentes que possam minimizar ou bloquear os efeitos tóxicos de Fe2+ e Cu2+. O extrato bruto de Peumus boldus, utilizado para o tratamento de desordens hepáticas, possui propriedades antioxidantes que já foram evidenciadas em diferentes modelos experimentais in vivo e in vitro, assim como a boldina, principal alcaloide isolado da planta. No entanto, os possíveis efeitos farmacológicos de P. boldus sobre a hepatotoxicidade induzida por Fe2+, bem como a possível ação protetora contra a toxicidade induzida por Cu2+, ainda não foram explorados. Da mesma forma, ainda não há pesquisas com P. boldus e toxicidade induzida por Cu2+ usando a Drosophila melanogaster como modelo experimental. Além das vantagens em termos de custeio e manutenção, D. melanogaster é uma espécie bastante confiável para estudos toxicológicos, uma vez que possui genes relacionados com a homeostase de Cu2+ que são altamente conservados em mamíferos. Assim, este trabalho teve como objetivo avaliar o possível efeito protetor de P.boldus e boldina contra o dano oxidativo hepático induzido por Fe2+, utilizando mitocôndrias de fígado de rato in vitro. Além disso, os efeitos oriundos da suplementação com P.boldus sobre alterações comportamentais, bioquímicas e moleculares induzidas por Cu2+ em D. melanogaster também foram testadas. De forma geral, verificamos que P.boldus foi mais eficiente que a boldina em diminuir a peroxidação lipídica, a produção de espécies reativas de oxigênio (ERO) e o inchaço causado por Fe2+ em mitocôndrias hepáticas. Os ensaios de avaliação da capacidade antioxidante em sistemas não biológicos mostraram que P. boldus foi eficaz em quelar Fe2+, enquanto que boldina exibiu maior poder redutor. As moscas expostas ao Cu2+ apresentaram uma redução no desempenho locomotor, observado através do teste de escalada, que foi melhorado pelo tratamento com P. boldus. A exposição ao Cu2+ diminuiu a atividade das enzimas acetilcolinesterase (AChE) e glutationa-S-tranferase (GST), que foram revertidas aos níveis do controle pelo tratamento com P. boldus. O Cu2+ causou um aumento na expressão de mRNA das enzimas superóxido dismutase (Sod1), catalase (Cat), tioredoxina redutase (TrxR1), fator nuclear eritróide 2 (Nrf2), acetilcolinesterase (Ace) e dos transportadores de Cu2+, ATPase do tipo P (Atp7A) e proteína de absorção de cobre 1 (Ctr1A). As alterações observadas na expressão do mRNA foram protegidas pelo tratamento com P.boldus. Em conjunto, os dados obtidos mostram que P.boldus é uma planta promissora para modular a toxicidade de Fe2+ e Cu2+, e que o extrato de P.boldus e boldina isolada têm propriedades antioxidantes, que podem atuar em doenças hepáticas associadas ao Fe2+ livre e ao EO. Esses resultados contribuem para o avanço das pesquisas na área de toxicologia e farmacologia de produtos naturais, bem como para a triagem de agentes terapêuticos promissores para tratar intoxicações ou doenças autossômicas associadas com o acúmulo de Fe2+ e Cu2+.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/openAccessP. boldusBoldinaReação de FentonEstresse oxidativoFerroCobreMitocôndriasDrosophila melanogasterDefesa antioxidanteBoldineFenton reactionOxidative stressIronCopperMitochondriaAntioxidant defensesCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAvaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentaisEvaluation of therapeutic potential of Peumus boldus (boldo) aqueous extract against toxicity induced by iron and copper in different experimental modelsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisRocha, João Batista Teixeira dahttp://lattes.cnpq.br/3935055744673018Barbosa, Nilda Berenice de Vargashttp://lattes.cnpq.br/5901511067144019Posser, Thaishttp://lattes.cnpq.br/2277857386983441Loreto, Elgion Lucio da Silvahttp://lattes.cnpq.br/6493669115018157Dalla Corte, Cristiane Lenzhttp://lattes.cnpq.br/5296284169605317Puntel, Robson Luizhttp://lattes.cnpq.br/1134532326779900http://lattes.cnpq.br/4037807722919397Klimaczewski, Cláudia Vargas200800000002600179568ac-3423-4e25-b5d9-d8fe8f55fc524b4381c9-25a3-482f-9a62-19e056f5635a25d9ca36-5752-4f7a-8b78-3152e2f2b159eed9356b-ea51-4cc4-9762-8e3a7b7e38f5ab41f5b8-3dea-4caa-86ab-c37a1044a37980e20f12-ebef-4233-a798-92a139af248cb3ebb44a-3bf1-4a63-849e-0437a5eab459reponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCBBT_2018_KLIMACZEWSKI_CLAUDIA.pdfTES_PPGCBBT_2018_KLIMACZEWSKI_CLAUDIA.pdfTese de Doutoradoapplication/pdf3982581http://repositorio.ufsm.br/bitstream/1/16714/1/TES_PPGCBBT_2018_KLIMACZEWSKI_CLAUDIA.pdf18b95d47c73bd8e6c80968fd848e9445MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais |
dc.title.alternative.eng.fl_str_mv |
Evaluation of therapeutic potential of Peumus boldus (boldo) aqueous extract against toxicity induced by iron and copper in different experimental models |
title |
Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais |
spellingShingle |
Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais Klimaczewski, Cláudia Vargas P. boldus Boldina Reação de Fenton Estresse oxidativo Ferro Cobre Mitocôndrias Drosophila melanogaster Defesa antioxidante Boldine Fenton reaction Oxidative stress Iron Copper Mitochondria Antioxidant defenses CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais |
title_full |
Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais |
title_fullStr |
Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais |
title_full_unstemmed |
Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais |
title_sort |
Avaliação do potencial terapêutico do extrato aquoso de Peumus boldus (boldo) frente à toxicidade induzida por ferro e cobre em diferentes modelos experimentais |
author |
Klimaczewski, Cláudia Vargas |
author_facet |
Klimaczewski, Cláudia Vargas |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Rocha, João Batista Teixeira da |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/3935055744673018 |
dc.contributor.advisor-co1.fl_str_mv |
Barbosa, Nilda Berenice de Vargas |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/5901511067144019 |
dc.contributor.referee1.fl_str_mv |
Posser, Thais |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/2277857386983441 |
dc.contributor.referee2.fl_str_mv |
Loreto, Elgion Lucio da Silva |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/6493669115018157 |
dc.contributor.referee3.fl_str_mv |
Dalla Corte, Cristiane Lenz |
dc.contributor.referee3Lattes.fl_str_mv |
http://lattes.cnpq.br/5296284169605317 |
dc.contributor.referee4.fl_str_mv |
Puntel, Robson Luiz |
dc.contributor.referee4Lattes.fl_str_mv |
http://lattes.cnpq.br/1134532326779900 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4037807722919397 |
dc.contributor.author.fl_str_mv |
Klimaczewski, Cláudia Vargas |
contributor_str_mv |
Rocha, João Batista Teixeira da Barbosa, Nilda Berenice de Vargas Posser, Thais Loreto, Elgion Lucio da Silva Dalla Corte, Cristiane Lenz Puntel, Robson Luiz |
dc.subject.por.fl_str_mv |
P. boldus Boldina Reação de Fenton Estresse oxidativo Ferro Cobre Mitocôndrias Drosophila melanogaster Defesa antioxidante |
topic |
P. boldus Boldina Reação de Fenton Estresse oxidativo Ferro Cobre Mitocôndrias Drosophila melanogaster Defesa antioxidante Boldine Fenton reaction Oxidative stress Iron Copper Mitochondria Antioxidant defenses CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Boldine Fenton reaction Oxidative stress Iron Copper Mitochondria Antioxidant defenses |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
The transition metals iron (Fe2+) and copper (Cu2+) are vital trace elements due to oxi-reducing properties. However, the free Fe2+ and Cu2+ accumulation can lead to oxidative stress (OS), by catalisis the Fenton reaction. The OS can lead to damage in biological macromolecules and is involved in the etiology of various pathologies, especially in liver and central nervous system (CNS), where Fe2+ and Cu2+ accumulates. Therefore, there is a growing interest for agents able to minimize or block the toxic effects of Fe2+and Cu2+. The Peumus boldus extract, used for the treatment of liver disorders, has shown antioxidant properties in different in vivo and in vitro experimental models, as well as boldine, the main alkaloid isolated from the plant. However, the pharmacological properties of P. boldus against Fe2+- induced hepatotoxicity, and Cu2+-induced toxicity, remains unexplored. Likewise, there is no data on the possible beneficial effects of P. boldus on the Cu2+ toxicity using Drosophila melanogaster as an experimental model, a specie widely used due to the fact of sharing well conserved genes with mammals such as those related to Cu2+ homeostasis. Thus, the main objective of this study was to evaluate the possible protective effect of P. boldus and boldine against Fe2+-induced hepatic oxidative damage in vitro using rat liver mitochondria, and the effect of P. boldus supplementation on molecular alterations induced by exposure to Cu2+ in D. melanogaster, in vivo and ex vivo. The results show that P.boldus aqueous extract was more efficient than boldine in decreasing the lipid peroxidation, the reactive oxygen species (ROS) production, and swelling induced by Fe2+ in hepatic mitochondria of rats. The antioxidant activity assays in non-biological systems showed that P. boldus was effective in chelating Fe2+, whereas boldine presented higher reducing power than P. boldus. Cu2+ impaired in the negative geotaxis performance (i.e. motor climbing capability), but P. boldus co-exposure was effective to protect against the Cu2+-induced toxicity. Acetylcholinesterase (AChE) and glutathione S-transferase (GST) activity decreased significantly in D. melanogaster after Cu2+ exposure. P. boldus co-treatment restored enzyme activities to control levels. In addition, Cu2+ exposure increased the mRNA levels of the enzymes, superoxide dismutase (Sod1), catalase (Cat), thioredoxin reductase (TrxR1), nuclear factor erythroid 2– related factor 2 (Nrf2), acetylcholinesterase (Ace) and Cu2+ transporters, P-type ATPase (Atp7A) and copper uptake protein 1 (Ctr1A). These alterations were restored to control levels by co-treatment with P.boldus. These findings suggest that P. boldus could be considered a promising plant in modulation of toxicity induced by an excess of Fe2+ and Cu2+. P.boldus and boldine can have antioxidant properties in protection against hepatic diseases associated with Fe-free and OS. In summary, these results contribute to the advancement of the investigations of agents that may in the assist therapy of intoxications or autosomal diseases linked to an excess of Fe2+ and Cu2+. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-08-10 |
dc.date.accessioned.fl_str_mv |
2019-05-31T16:14:33Z |
dc.date.available.fl_str_mv |
2019-05-31T16:14:33Z |
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.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/16714 |
url |
http://repositorio.ufsm.br/handle/1/16714 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 |
dc.relation.authority.fl_str_mv |
179568ac-3423-4e25-b5d9-d8fe8f55fc52 4b4381c9-25a3-482f-9a62-19e056f5635a 25d9ca36-5752-4f7a-8b78-3152e2f2b159 eed9356b-ea51-4cc4-9762-8e3a7b7e38f5 ab41f5b8-3dea-4caa-86ab-c37a1044a379 80e20f12-ebef-4233-a798-92a139af248c b3ebb44a-3bf1-4a63-849e-0437a5eab459 |
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 |
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 |
bitstream.url.fl_str_mv |
http://repositorio.ufsm.br/bitstream/1/16714/1/TES_PPGCBBT_2018_KLIMACZEWSKI_CLAUDIA.pdf http://repositorio.ufsm.br/bitstream/1/16714/2/license_rdf http://repositorio.ufsm.br/bitstream/1/16714/3/license.txt http://repositorio.ufsm.br/bitstream/1/16714/4/TES_PPGCBBT_2018_KLIMACZEWSKI_CLAUDIA.pdf.txt http://repositorio.ufsm.br/bitstream/1/16714/5/TES_PPGCBBT_2018_KLIMACZEWSKI_CLAUDIA.pdf.jpg |
bitstream.checksum.fl_str_mv |
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bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
|
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1794524403173687296 |