Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/11136 |
Resumo: | Recent data from the literature have suggested that some Krebs cycle intermediates could act as potent antioxidant agents, both in vitro and in vivo, against a variety of pro-oxidant agents. However, the mechanism(s) involved in the antioxidant effect of Krebs cycle intermediates are not fully understood. Additionally, there are scarce data in the literature taking into account the in vitro effect of Krebs cycle intermediates during oxidative stress conditions. Thus, the aim of this study was to determine the effect of some Krebs cycle intermediates on lipid peroxidation induced in vitro by different pro-oxidant agents, and the mechanism(s) by which they act. Firstly, we investigated the effect and the mechanism(s) by which malonate and quinolinic acid modulate the thiobarbituric acid- reactive species (TBARS) production in vitro, using rat brain S1 preparations (Article 1). The present results showed that the malonate-induced TBARS production was not changed by potassium cyanide or MK-801. However, the pro-oxidant effect of quinolinic acid was significantly prevented by MK-801. In addition we found that malonate was able to form complexes with iron ions (Fe2+), but these complexes were not able to interfere with in vitro deoxyribose degradation assays. Based on the results presented, we conclude that malonate pro-oxidant activity in vitro seems to be independent of the NMDA receptors activity. Additionally, we suggest that the malonate effect, in these conditions, is due to its ability to form complexes with iron ions, thus modulating an adequate ratio Fe2+/Fe3+ that could cause an increase in free radicals generation. In contrast, the quinolinic acid effect seems to be dependent of the NMDA receptors activation. However, we can not rule out the involvement of iron ions in quinolinic acid toxicity under our assay conditions. An other objective of this study was to investigate the effect of some Krebs cycle intermediates on quinolinic acid- or iron (Fe2+)-induced TBARS production in the rat brain S1 preparations, and the mechanism(s) by which they act (Article 2). The results showed that oxaloacetate, citrate, succinate, and malate were able to significantly prevent both basal and quinolinic acid- or iron-induced TBARS production. However, α-ketoglutarate induced per se a significant increase in basal TBARS production. The addition of potassium cyanide or the heat-treatment of S1 at 100ºC during 10 min completely abolished the antioxidant succinate activity, without change the effect of other Krebs cycle intermediates studied. Except for succinate, all intermediates used in this study were able to form complexes with iron (Fe2+) ions, however only oxaloacetate and α-ketoglutarate significantly prevented deoxyribose degradation induced by hydrogen peroxide. Based on the results presented, we concluded that oxaloacetate, malate, succinate, and citrate could act as antioxidants under basal, and under quinolinic acid- or iron- induced TBARS production, whereas α-ketoglutarate act as a pro-oxidant agent per se. The mechanism(s) by which citrate, malate, and oxaloacetate acts seems to be related to their ability to form complexes with iron (Fe2+) ions, thus modulating the iron redox cycle. In contrast, the succinate antioxidant effect seems to be dependent of the succinate dehydrogenase (SDH) activity. |
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Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantesEffect of krebs cycle intermediates on oxidative changes induced by different oxidant agentsIntermediários do ciclo de KrebsMalonatoÁcido quinolínicoFerroE peroxidação lipídicaKrebs cycle intermediatesMalonateQuinolinic acidIron and lipid proxidationCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICARecent data from the literature have suggested that some Krebs cycle intermediates could act as potent antioxidant agents, both in vitro and in vivo, against a variety of pro-oxidant agents. However, the mechanism(s) involved in the antioxidant effect of Krebs cycle intermediates are not fully understood. Additionally, there are scarce data in the literature taking into account the in vitro effect of Krebs cycle intermediates during oxidative stress conditions. Thus, the aim of this study was to determine the effect of some Krebs cycle intermediates on lipid peroxidation induced in vitro by different pro-oxidant agents, and the mechanism(s) by which they act. Firstly, we investigated the effect and the mechanism(s) by which malonate and quinolinic acid modulate the thiobarbituric acid- reactive species (TBARS) production in vitro, using rat brain S1 preparations (Article 1). The present results showed that the malonate-induced TBARS production was not changed by potassium cyanide or MK-801. However, the pro-oxidant effect of quinolinic acid was significantly prevented by MK-801. In addition we found that malonate was able to form complexes with iron ions (Fe2+), but these complexes were not able to interfere with in vitro deoxyribose degradation assays. Based on the results presented, we conclude that malonate pro-oxidant activity in vitro seems to be independent of the NMDA receptors activity. Additionally, we suggest that the malonate effect, in these conditions, is due to its ability to form complexes with iron ions, thus modulating an adequate ratio Fe2+/Fe3+ that could cause an increase in free radicals generation. In contrast, the quinolinic acid effect seems to be dependent of the NMDA receptors activation. However, we can not rule out the involvement of iron ions in quinolinic acid toxicity under our assay conditions. An other objective of this study was to investigate the effect of some Krebs cycle intermediates on quinolinic acid- or iron (Fe2+)-induced TBARS production in the rat brain S1 preparations, and the mechanism(s) by which they act (Article 2). The results showed that oxaloacetate, citrate, succinate, and malate were able to significantly prevent both basal and quinolinic acid- or iron-induced TBARS production. However, α-ketoglutarate induced per se a significant increase in basal TBARS production. The addition of potassium cyanide or the heat-treatment of S1 at 100ºC during 10 min completely abolished the antioxidant succinate activity, without change the effect of other Krebs cycle intermediates studied. Except for succinate, all intermediates used in this study were able to form complexes with iron (Fe2+) ions, however only oxaloacetate and α-ketoglutarate significantly prevented deoxyribose degradation induced by hydrogen peroxide. Based on the results presented, we concluded that oxaloacetate, malate, succinate, and citrate could act as antioxidants under basal, and under quinolinic acid- or iron- induced TBARS production, whereas α-ketoglutarate act as a pro-oxidant agent per se. The mechanism(s) by which citrate, malate, and oxaloacetate acts seems to be related to their ability to form complexes with iron (Fe2+) ions, thus modulating the iron redox cycle. In contrast, the succinate antioxidant effect seems to be dependent of the succinate dehydrogenase (SDH) activity.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorDados recentes na literatura têm relatado que alguns intermediários do ciclo de Krebs podem agir como potentes antioxidantes, tanto in vitro, quanto in vivo, em diversos sistemas pró-oxidantes. Porém, o(s) mecanismo(s) através dos qual(is) os intermediários do ciclo de Krebs exercem suas atividades antioxidantes não são completamente entendidas. Considerando a escassez de dados in vitro na literatura a respeito do efeito desses intermediários durante situações de estresse oxidativo, o presente trabalho tem como objetivo determinar o efeito de intermediários do ciclo de Krebs sob a peroxidação lipídica induzida por diferentes agentes pró-oxidantes in vitro, bem como investigar o(s) mecanismo(s) de ação dos mesmos. Primeiramente investigamos o efeito e o(s) mecanismo(s) pelo(s) qual(is) o malonato e o ácido quinolínico modulam a produção de espécies reativas ao ácido tiobarbitúrico (TBARS) em S1 de cérebro de ratos, in vitro (artigo 1). Os resultados obtidos mostraram um aumento na produção de TBARS induzido pelo malonato, o qual não foi modificado pela adição de cianeto de potássio, nem pelo MK-801. Por outro lado, o efeito pró-oxidante do ácido quinolínico foi significativamente prevenido pelo MK-801. Observamos ainda que o malonato foi capaz de formar complexos com íons ferrosos e que esses complexos não foram capazes de interferir nos ensaios da degradação da desoxirribose in vitro. Portanto, com base nos resultados encontrados, concluímos que o efeito pró-oxidante do malonato in vitro parece ser independente da atividade dos receptores NMDA. Os resultados sugerem que o efeito do malonato nessas condições deve-se principalmente a sua capacidade de interagir com íons ferro, modulando uma razão Fe2+/Fe3+ que favorece a geração de radicais livres. Por outro lado, o efeito do ácido quinolínico parece ser devido à ativação dos receptores NMDA. Porém, não podemos excluir a participação dos íons ferro para a toxicidade do mesmo nessas condições. Outro foco deste estudo foi investigar o efeito de alguns intermediários do ciclo de Krebs na produção de TBARS induzida por ácido quinolínico ou ferro em S1 de cérebro de ratos in vitro, bem como investigar o(s) mecanismo(s) de ação dos mesmos (artigo 2). Os resultados mostraram que o oxaloacetato, o citrato, o sucinato e o malato foram capazes de reduzir significativamente a produção de TBARS basal, bem como a induzida por ácido quinolínico ou ferro. Por outro lado, o α-cetoglutarato foi capaz de induzir per se um significativo aumento na produção de TBARS. A adição de cianeto de potássio, bem como o pré-tratamento do S1 por 10 min a 100ºC aboliram completamente o efeito antioxidante do sucinato, sem interferir significativamente no efeito dos demais intermediários estudados. Todos os intermediários estudados, exceto o sucinato, foram capazes de quelar íons ferro, porém somente o oxaloacetato e o α-cetoglutarato foram capazes de prevenir a degradação da desoxirribose induzida por peróxido de hidrogênio. Com base nos resultados obtidos, podemos concluir que o oxaloacetato, o malato o sucinato e o citrato agem como antioxidantes sob condições basais ou em presença do ácido quinolínico ou ferro, enquanto que o α-cetoglutarato age como um agente pró-oxidante per se. O mecanismo pelo qual o citrato, o malato e o oxaloacetato exercem seus efeitos antioxidantes parece ser devido à capacidade desses em interagir com íons ferro modulando o ciclo redox desse. Por outro lado, o efeito do sucinato parece ser devido à atividade da enzima succinato desidrogenase (SDH).Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Rocha, João Batista Teixeira dahttp://lattes.cnpq.br/3935055744673018Souza, Diogo Onofre Gomes dehttp://lattes.cnpq.br/9534019126486839Ferreira, Julianohttp://lattes.cnpq.br/2694197910478313Puntel, Robson Luiz2017-04-262017-04-262006-10-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfapplication/pdfapplication/pdfPUNTEL, Robson Luiz. Effect of krebs cycle intermediates on oxidative changes induced by different oxidant agents. 2006. 71 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2006.http://repositorio.ufsm.br/handle/1/11136porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2023-01-26T19:58:41Zoai:repositorio.ufsm.br:1/11136Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-01-26T19:58:41Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes Effect of krebs cycle intermediates on oxidative changes induced by different oxidant agents |
title |
Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes |
spellingShingle |
Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes Puntel, Robson Luiz Intermediários do ciclo de Krebs Malonato Ácido quinolínico Ferro E peroxidação lipídica Krebs cycle intermediates Malonate Quinolinic acid Iron and lipid proxidation CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes |
title_full |
Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes |
title_fullStr |
Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes |
title_full_unstemmed |
Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes |
title_sort |
Efeito de intermediários do ciclo de krebs sobre alterações oxidativas induzidas por diferentes agentes oxidantes |
author |
Puntel, Robson Luiz |
author_facet |
Puntel, Robson Luiz |
author_role |
author |
dc.contributor.none.fl_str_mv |
Nogueira, Cristina Wayne http://lattes.cnpq.br/2877042401245169 Rocha, João Batista Teixeira da http://lattes.cnpq.br/3935055744673018 Souza, Diogo Onofre Gomes de http://lattes.cnpq.br/9534019126486839 Ferreira, Juliano http://lattes.cnpq.br/2694197910478313 |
dc.contributor.author.fl_str_mv |
Puntel, Robson Luiz |
dc.subject.por.fl_str_mv |
Intermediários do ciclo de Krebs Malonato Ácido quinolínico Ferro E peroxidação lipídica Krebs cycle intermediates Malonate Quinolinic acid Iron and lipid proxidation CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Intermediários do ciclo de Krebs Malonato Ácido quinolínico Ferro E peroxidação lipídica Krebs cycle intermediates Malonate Quinolinic acid Iron and lipid proxidation CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Recent data from the literature have suggested that some Krebs cycle intermediates could act as potent antioxidant agents, both in vitro and in vivo, against a variety of pro-oxidant agents. However, the mechanism(s) involved in the antioxidant effect of Krebs cycle intermediates are not fully understood. Additionally, there are scarce data in the literature taking into account the in vitro effect of Krebs cycle intermediates during oxidative stress conditions. Thus, the aim of this study was to determine the effect of some Krebs cycle intermediates on lipid peroxidation induced in vitro by different pro-oxidant agents, and the mechanism(s) by which they act. Firstly, we investigated the effect and the mechanism(s) by which malonate and quinolinic acid modulate the thiobarbituric acid- reactive species (TBARS) production in vitro, using rat brain S1 preparations (Article 1). The present results showed that the malonate-induced TBARS production was not changed by potassium cyanide or MK-801. However, the pro-oxidant effect of quinolinic acid was significantly prevented by MK-801. In addition we found that malonate was able to form complexes with iron ions (Fe2+), but these complexes were not able to interfere with in vitro deoxyribose degradation assays. Based on the results presented, we conclude that malonate pro-oxidant activity in vitro seems to be independent of the NMDA receptors activity. Additionally, we suggest that the malonate effect, in these conditions, is due to its ability to form complexes with iron ions, thus modulating an adequate ratio Fe2+/Fe3+ that could cause an increase in free radicals generation. In contrast, the quinolinic acid effect seems to be dependent of the NMDA receptors activation. However, we can not rule out the involvement of iron ions in quinolinic acid toxicity under our assay conditions. An other objective of this study was to investigate the effect of some Krebs cycle intermediates on quinolinic acid- or iron (Fe2+)-induced TBARS production in the rat brain S1 preparations, and the mechanism(s) by which they act (Article 2). The results showed that oxaloacetate, citrate, succinate, and malate were able to significantly prevent both basal and quinolinic acid- or iron-induced TBARS production. However, α-ketoglutarate induced per se a significant increase in basal TBARS production. The addition of potassium cyanide or the heat-treatment of S1 at 100ºC during 10 min completely abolished the antioxidant succinate activity, without change the effect of other Krebs cycle intermediates studied. Except for succinate, all intermediates used in this study were able to form complexes with iron (Fe2+) ions, however only oxaloacetate and α-ketoglutarate significantly prevented deoxyribose degradation induced by hydrogen peroxide. Based on the results presented, we concluded that oxaloacetate, malate, succinate, and citrate could act as antioxidants under basal, and under quinolinic acid- or iron- induced TBARS production, whereas α-ketoglutarate act as a pro-oxidant agent per se. The mechanism(s) by which citrate, malate, and oxaloacetate acts seems to be related to their ability to form complexes with iron (Fe2+) ions, thus modulating the iron redox cycle. In contrast, the succinate antioxidant effect seems to be dependent of the succinate dehydrogenase (SDH) activity. |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006-10-30 2017-04-26 2017-04-26 |
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 |
PUNTEL, Robson Luiz. Effect of krebs cycle intermediates on oxidative changes induced by different oxidant agents. 2006. 71 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2006. http://repositorio.ufsm.br/handle/1/11136 |
identifier_str_mv |
PUNTEL, Robson Luiz. Effect of krebs cycle intermediates on oxidative changes induced by different oxidant agents. 2006. 71 f. Dissertação (Mestrado em Bioquímica) - Universidade Federal de Santa Maria, Santa Maria, 2006. |
url |
http://repositorio.ufsm.br/handle/1/11136 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
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 |
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1805922111809650688 |