Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos
Ano de defesa: | 2009 |
---|---|
Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
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/1/11099 |
Resumo: | The liver presents extraordinary functional diversity, particularly in the control of energy production, immune defense and volemic reserve. The human being is exposed occupationally and in the environment to a variety of hepatotoxic compounds, such as the use of paints and their derivatives (2-nitropropane, 2-NP), chemical reagents (carbon tetrachloride, CCl4) and exposure to cigarette (2-NP). Therefore, it is interesting the study of therapies to prevent or even reverse the poisoning caused by these compounds. Considering that reactive oxygen species (ROS) have an important role in various diseases, especially in liver diseases, the use of antioxidant therapies should be considered. In this context, the heterocyclic compounds containing selenium in their structures have attracted the attention of researchers. Thus, this study investigated the antioxidant activity of 3-alkynyl selenophenes in models of oxidative damage in vitro and ex vivo in rats (Wistar, male, weighing 200-300g). A class of 3-alkynyl selenophene compounds with different substitutions was tested, with the objective to assess their antioxidant profile and their possible toxic effect in vitro. As a result, 3-alkynyl selenophenes had antioxidant activity, but this activity was dependent on the presence of terminal alkynes in the molecule or easy conversion to it. The possible toxic effect of 3-alkynyl selenophenes was evaluated through the activity of the enzyme δ-aminolevulinate dehydratase (δ-ALA-D) in vitro. The results showed that none of 3-alkynyl selenophenes inhibited the activity of this enzyme, suggesting that this class of compound did not present toxicity on this enzyme. From these results, selenophene h (compound that had the best antioxidant activity in vitro) was selected for the evaluation of its protective effect against oxidative damage induced by 2-NP and CCl4 (ex vivo). Selenophene h (25 mg/kg) protected against the increase of markers of liver damage (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities) and oxidative stress induced by administration of 2-NP in rats. 2-NP induced microscopic changes, evaluated by histopathological inspections, that were protected by this compound. Selenophene h showed a protective effect against the increase of lipid peroxidation and inhibition of activity of δ-ALA-D in animals treated with 2-NP. Selenophene h protected against oxidative damage induced by CCl4 in rats. A single dose of CCl4 caused significant hepatotoxicity, evidenced by elevated plasma enzyme activity of AST and ALT, increased incidence of histopathological lesions, increased lipid peroxidation levels and the activity of Glutathione-S-transferase (GST), decreased levels of ascorbic acid and the activity of catalase and δ-ALA-D. In conclusion, 3-alkynyl selenophene protected from all these changes, confirming its hepatoprotective effect. Considering the results, we suggest that 3-alkynyl selenophene, an antioxidant, may be a useful therapy for the oxidative damage induced by 2-NP or CCl4 . |
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2017-04-242017-04-242009-02-16WILHELM, Ethel Antunes. Hepatoprotective effect of 3-alkynyl selenophene against oxidative damage induced by chemical inductors in rats. 2009. 113 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2009.http://repositorio.ufsm.br/handle/1/11099The liver presents extraordinary functional diversity, particularly in the control of energy production, immune defense and volemic reserve. The human being is exposed occupationally and in the environment to a variety of hepatotoxic compounds, such as the use of paints and their derivatives (2-nitropropane, 2-NP), chemical reagents (carbon tetrachloride, CCl4) and exposure to cigarette (2-NP). Therefore, it is interesting the study of therapies to prevent or even reverse the poisoning caused by these compounds. Considering that reactive oxygen species (ROS) have an important role in various diseases, especially in liver diseases, the use of antioxidant therapies should be considered. In this context, the heterocyclic compounds containing selenium in their structures have attracted the attention of researchers. Thus, this study investigated the antioxidant activity of 3-alkynyl selenophenes in models of oxidative damage in vitro and ex vivo in rats (Wistar, male, weighing 200-300g). A class of 3-alkynyl selenophene compounds with different substitutions was tested, with the objective to assess their antioxidant profile and their possible toxic effect in vitro. As a result, 3-alkynyl selenophenes had antioxidant activity, but this activity was dependent on the presence of terminal alkynes in the molecule or easy conversion to it. The possible toxic effect of 3-alkynyl selenophenes was evaluated through the activity of the enzyme δ-aminolevulinate dehydratase (δ-ALA-D) in vitro. The results showed that none of 3-alkynyl selenophenes inhibited the activity of this enzyme, suggesting that this class of compound did not present toxicity on this enzyme. From these results, selenophene h (compound that had the best antioxidant activity in vitro) was selected for the evaluation of its protective effect against oxidative damage induced by 2-NP and CCl4 (ex vivo). Selenophene h (25 mg/kg) protected against the increase of markers of liver damage (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities) and oxidative stress induced by administration of 2-NP in rats. 2-NP induced microscopic changes, evaluated by histopathological inspections, that were protected by this compound. Selenophene h showed a protective effect against the increase of lipid peroxidation and inhibition of activity of δ-ALA-D in animals treated with 2-NP. Selenophene h protected against oxidative damage induced by CCl4 in rats. A single dose of CCl4 caused significant hepatotoxicity, evidenced by elevated plasma enzyme activity of AST and ALT, increased incidence of histopathological lesions, increased lipid peroxidation levels and the activity of Glutathione-S-transferase (GST), decreased levels of ascorbic acid and the activity of catalase and δ-ALA-D. In conclusion, 3-alkynyl selenophene protected from all these changes, confirming its hepatoprotective effect. Considering the results, we suggest that 3-alkynyl selenophene, an antioxidant, may be a useful therapy for the oxidative damage induced by 2-NP or CCl4 .O fígado apresenta extraordinária pluralidade funcional, destacando-se no controle de produção de energia, defesa imunológica e reserva volêmica. No meio ambiente e ocupacionalmente, o ser humano está exposto a uma variedade de compostos hepatotóxicos, como por exemplo, no uso de tintas e seus derivados (2-nitropropano, 2- NP), reagentes químicos (tetracloreto de carbono, CCl4) e na exposição ao cigarro (2-NP). Portanto, é interessante o estudo de terapias que previnam ou até mesmo revertam a intoxicação causada por estes compostos. Considerando que as espécies reativas de oxigênio (EROs) apresentam importante papel sobre diversas patologias, em especial nas doenças hepáticas, o uso de terapias antioxidantes deve ser considerada. Neste contexto, destacam-se os compostos heterocíclicos contendo selênio em sua estrutura. Deste modo, neste estudo investigou-se a atividade antioxidante de 3-alquinil selenofenos em modelos de dano oxidativo in vitro e ex vivo em ratos (Wistar, machos, pesando entre 200 300 g). Para esse fim, testou-se uma classe de compostos 3-alquinil selenofeno, com diferentes substituições na estrutura química, com o objetivo de avaliar o perfil antioxidante e seu possível efeito tóxico in vitro em ratos. Como resultado, 3- alquinil selenofenos tiveram atividade antioxidante, porém esta atividade foi dependente da presença de um alquino terminal na molécula ou da fácil conversão da molécula a um alquino terminal. Além disso, o possível efeito tóxico dos 3-alquinil selenofenos foi avaliado através da atividade da enzima δ-aminolevulinato desidratase (δ-ALA-D) in vitro. Os resultados obtidos demonstraram que nenhum dos 3-alquinil selenofenos testados inibiu a atividade desta enzima, sugerindo que esta classe de compostos não apresentou toxicidade sobre a atividade da δ-ALA-D. A partir destes resultados, selecionou-se o selenofeno h (que obteve melhor atividade antioxidante in vitro) para a avaliação do seu efeito protetor contra o dano oxidativo induzido por 2-NP e CCl4 em ratos (ex vivo). O selenofeno h (25 mg/kg) protegeu contra o aumento dos marcadores de dano hepático (aspartato aminotranferase (AST) e alanina aminotransferase (ALT)) e de estresse oxidativo induzidos pela administração do 2-NP. O 2-NP induziu alterações microscópicas avaliadas por inspeções histopatológicas as quais foram protegidas pelo composto. O selenofeno h demonstrou efeito protetor contra o aumento da peroxidação lipídica e inibição da atividade da δ-ALA-D nos animais tratados com 2-NP. Além disso, o selenofeno h protegeu contra o dano oxidativo induzido pelo CCl4 em ratos. Uma única dose de CCl4 causou significante hepatotoxicidade, evidenciada por elevação da atividade plasmática das enzimas AST e ALT, aumento da incidência de lesões histopatológicas, aumento dos níveis de peroxidação lipídica e da atividade da enzima glutationa-S-transferase (GST), bem como diminuição dos níveis de ácido ascórbico e da atividade das enzimas catalase e δ-ALA-D. A partir dos resultados demonstrados, verificou-se que o selenofeno h protegeu contra todas estas alterações, confirmando o seu efeito hepatoprotetor. Considerando os resultados obtidos, pode-se sugerir que o selenofeno h, uma molécula com atividade antioxidante, pode ser uma útil terapia contra o dano oxidativo induzido pelos hepatotoxicantes: 2-NP e CCl4.Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaDano hepáticoSelênio3-alquinil selenofenoTetracloreto de carbono2-nitropropanoLiver damageSelenium3-alkynyl selenopheneCarbon tetrachloride2-nitropropaneCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratosHepatoprotective effect of 3-alkynyl selenophene against oxidative damage induced by chemical inductors in ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisSavegnago, Luciellihttp://lattes.cnpq.br/1480751214999787Nogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Bonan, Carla Denisehttp://lattes.cnpq.br/8058052532279136Mazzanti, Alexandrehttp://lattes.cnpq.br/3504517995843014http://lattes.cnpq.br/2247558205680051Wilhelm, Ethel Antunes20080000000240030050050050050065ce32cc-e378-45c4-9df2-c7f9e84e4a105429cb10-b01f-474c-a666-4ccf3881a854c2b1a64f-5f22-4779-9732-0c543f42b42d64d05617-eaff-4cb5-8519-d7dc8a4679329a05d168-7f5c-4d8b-a845-579aa89980c2info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALETHELANTUNESWILHELM.pdfapplication/pdf694621http://repositorio.ufsm.br/bitstream/1/11099/1/ETHELANTUNESWILHELM.pdf2c3063fe1d073f0c5a88ffc5ab71815aMD51TEXTETHELANTUNESWILHELM.pdf.txtETHELANTUNESWILHELM.pdf.txtExtracted texttext/plain172284http://repositorio.ufsm.br/bitstream/1/11099/2/ETHELANTUNESWILHELM.pdf.txtc7000c2fdf0336bb6cf9f74ee2d07bb8MD52THUMBNAILETHELANTUNESWILHELM.pdf.jpgETHELANTUNESWILHELM.pdf.jpgIM Thumbnailimage/jpeg5950http://repositorio.ufsm.br/bitstream/1/11099/3/ETHELANTUNESWILHELM.pdf.jpg5b09a693b5c083cf1a4e1868c54acc2aMD531/110992023-05-03 09:23:17.132oai:repositorio.ufsm.br:1/11099Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-05-03T12:23:17Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos |
dc.title.alternative.eng.fl_str_mv |
Hepatoprotective effect of 3-alkynyl selenophene against oxidative damage induced by chemical inductors in rats |
title |
Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos |
spellingShingle |
Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos Wilhelm, Ethel Antunes Dano hepático Selênio 3-alquinil selenofeno Tetracloreto de carbono 2-nitropropano Liver damage Selenium 3-alkynyl selenophene Carbon tetrachloride 2-nitropropane CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos |
title_full |
Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos |
title_fullStr |
Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos |
title_full_unstemmed |
Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos |
title_sort |
Efeito hepatoprotetor causado pelo 3-alquinil selenofeno contra o dano oxidativo induzido por agentes químicos em ratos |
author |
Wilhelm, Ethel Antunes |
author_facet |
Wilhelm, Ethel Antunes |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Savegnago, Lucielli |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1480751214999787 |
dc.contributor.advisor-co1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/2877042401245169 |
dc.contributor.referee1.fl_str_mv |
Bonan, Carla Denise |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/8058052532279136 |
dc.contributor.referee2.fl_str_mv |
Mazzanti, Alexandre |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/3504517995843014 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/2247558205680051 |
dc.contributor.author.fl_str_mv |
Wilhelm, Ethel Antunes |
contributor_str_mv |
Savegnago, Lucielli Nogueira, Cristina Wayne Bonan, Carla Denise Mazzanti, Alexandre |
dc.subject.por.fl_str_mv |
Dano hepático Selênio 3-alquinil selenofeno Tetracloreto de carbono 2-nitropropano |
topic |
Dano hepático Selênio 3-alquinil selenofeno Tetracloreto de carbono 2-nitropropano Liver damage Selenium 3-alkynyl selenophene Carbon tetrachloride 2-nitropropane CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Liver damage Selenium 3-alkynyl selenophene Carbon tetrachloride 2-nitropropane |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
The liver presents extraordinary functional diversity, particularly in the control of energy production, immune defense and volemic reserve. The human being is exposed occupationally and in the environment to a variety of hepatotoxic compounds, such as the use of paints and their derivatives (2-nitropropane, 2-NP), chemical reagents (carbon tetrachloride, CCl4) and exposure to cigarette (2-NP). Therefore, it is interesting the study of therapies to prevent or even reverse the poisoning caused by these compounds. Considering that reactive oxygen species (ROS) have an important role in various diseases, especially in liver diseases, the use of antioxidant therapies should be considered. In this context, the heterocyclic compounds containing selenium in their structures have attracted the attention of researchers. Thus, this study investigated the antioxidant activity of 3-alkynyl selenophenes in models of oxidative damage in vitro and ex vivo in rats (Wistar, male, weighing 200-300g). A class of 3-alkynyl selenophene compounds with different substitutions was tested, with the objective to assess their antioxidant profile and their possible toxic effect in vitro. As a result, 3-alkynyl selenophenes had antioxidant activity, but this activity was dependent on the presence of terminal alkynes in the molecule or easy conversion to it. The possible toxic effect of 3-alkynyl selenophenes was evaluated through the activity of the enzyme δ-aminolevulinate dehydratase (δ-ALA-D) in vitro. The results showed that none of 3-alkynyl selenophenes inhibited the activity of this enzyme, suggesting that this class of compound did not present toxicity on this enzyme. From these results, selenophene h (compound that had the best antioxidant activity in vitro) was selected for the evaluation of its protective effect against oxidative damage induced by 2-NP and CCl4 (ex vivo). Selenophene h (25 mg/kg) protected against the increase of markers of liver damage (aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities) and oxidative stress induced by administration of 2-NP in rats. 2-NP induced microscopic changes, evaluated by histopathological inspections, that were protected by this compound. Selenophene h showed a protective effect against the increase of lipid peroxidation and inhibition of activity of δ-ALA-D in animals treated with 2-NP. Selenophene h protected against oxidative damage induced by CCl4 in rats. A single dose of CCl4 caused significant hepatotoxicity, evidenced by elevated plasma enzyme activity of AST and ALT, increased incidence of histopathological lesions, increased lipid peroxidation levels and the activity of Glutathione-S-transferase (GST), decreased levels of ascorbic acid and the activity of catalase and δ-ALA-D. In conclusion, 3-alkynyl selenophene protected from all these changes, confirming its hepatoprotective effect. Considering the results, we suggest that 3-alkynyl selenophene, an antioxidant, may be a useful therapy for the oxidative damage induced by 2-NP or CCl4 . |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-02-16 |
dc.date.accessioned.fl_str_mv |
2017-04-24 |
dc.date.available.fl_str_mv |
2017-04-24 |
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info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
WILHELM, Ethel Antunes. Hepatoprotective effect of 3-alkynyl selenophene against oxidative damage induced by chemical inductors in rats. 2009. 113 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/11099 |
identifier_str_mv |
WILHELM, Ethel Antunes. Hepatoprotective effect of 3-alkynyl selenophene against oxidative damage induced by chemical inductors in rats. 2009. 113 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2009. |
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http://repositorio.ufsm.br/handle/1/11099 |
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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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Bioquímica |
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Universidade Federal de Santa Maria |
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