Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20451 |
Resumo: | Aspartame is a synthetic sweetener widely used by individuals with restriction diets of sucrose, glucose or fructose or by those seeking wight loss. Several studies have indicated that its use is related to changes in the central nervous system, as well as to the induction of oxidative stress. However, the mechanisms responsible for such effects are not fully understood, as well as the potential of antioxidant compounds, such as N-acetylcysteine, in mitigating such damages. Thus, this study evaluated the effects of N-acetylcysteine (NAC) (163 mg/kg, i.p) on behavioral and oxidative parameters against the long-term (90 days) administration of aspartame (80 mg/kg, v.o) in brain regions of mice. For this purpose, Swiss albino male mice were divided in three groups: control – received both aspartame and Nacetylcysteine vehicles; ASP – received aspartame, and the N-acetylcysteine vehicle; and ASP-NAC – received both treatments, aspartame and N-acetylcysteine. Aspartame was administered for 90 days, while NAC was injected only in the last 30 days. In the last week of the experimental period, the animals had their behavior evaluated through the open field test. At the end of the 90 days, the animals were anesthetized and euthanized for the removal of the brain and separation of the following regions: cerebral cortex, hippocampus and cerebellum, in which was held the research of the oxidative stress biomarkers and the gene expression of catalytic subunit of glutamate cysteine ligase (Gclc), cystathionin γ-lyase (Cth) and thioredoxin 1 (Trx1). The results showed that the mice treated with aspartame and NAC presented a decrease in the number of crossings and an increase in the time spent in the central area in relation to the control animals and treated with aspartame alone. Although it did not alter the thioredoxin system, the administration of aspartame caused severe depletion in non-protein thiois (NPSH) levels as well as glutathione peroxidase (GPx) activity. Both changes were restored by treatment with NAC. Aspartame also triggered a decrease in Gclc and Cth mRNA levels. Treatment with NAC restored Gclc levels. It is concluded from these results that, although it did not alter the thioredoxin system, treatment with aspartame caused a severe depletion of NPSH levels, which may be due to the decrease in Gclc and Cth mRNA levels, demonstrating that the mechanism of action of aspartame toxicity is more related to the GSH system. In addition, the results suggest an anxiolytic effect of NAC in animals treated with aspartame. NAC was able to restore most of the changes in the GSH-related system in brain regions after long-term ingestion of aspartame. |
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Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartameN-acetylcysteine evaluation on behavioral and oxidative parameters front long term administration of aspartameGlutationaAdoçantes de baixa caloriaTiorredoxinaRegiões cerebraisGlutathioneLow-calorie sweetenersTioredoxinBrain regionsCNPQ::CIENCIAS DA SAUDE::FARMACIAAspartame is a synthetic sweetener widely used by individuals with restriction diets of sucrose, glucose or fructose or by those seeking wight loss. Several studies have indicated that its use is related to changes in the central nervous system, as well as to the induction of oxidative stress. However, the mechanisms responsible for such effects are not fully understood, as well as the potential of antioxidant compounds, such as N-acetylcysteine, in mitigating such damages. Thus, this study evaluated the effects of N-acetylcysteine (NAC) (163 mg/kg, i.p) on behavioral and oxidative parameters against the long-term (90 days) administration of aspartame (80 mg/kg, v.o) in brain regions of mice. For this purpose, Swiss albino male mice were divided in three groups: control – received both aspartame and Nacetylcysteine vehicles; ASP – received aspartame, and the N-acetylcysteine vehicle; and ASP-NAC – received both treatments, aspartame and N-acetylcysteine. Aspartame was administered for 90 days, while NAC was injected only in the last 30 days. In the last week of the experimental period, the animals had their behavior evaluated through the open field test. At the end of the 90 days, the animals were anesthetized and euthanized for the removal of the brain and separation of the following regions: cerebral cortex, hippocampus and cerebellum, in which was held the research of the oxidative stress biomarkers and the gene expression of catalytic subunit of glutamate cysteine ligase (Gclc), cystathionin γ-lyase (Cth) and thioredoxin 1 (Trx1). The results showed that the mice treated with aspartame and NAC presented a decrease in the number of crossings and an increase in the time spent in the central area in relation to the control animals and treated with aspartame alone. Although it did not alter the thioredoxin system, the administration of aspartame caused severe depletion in non-protein thiois (NPSH) levels as well as glutathione peroxidase (GPx) activity. Both changes were restored by treatment with NAC. Aspartame also triggered a decrease in Gclc and Cth mRNA levels. Treatment with NAC restored Gclc levels. It is concluded from these results that, although it did not alter the thioredoxin system, treatment with aspartame caused a severe depletion of NPSH levels, which may be due to the decrease in Gclc and Cth mRNA levels, demonstrating that the mechanism of action of aspartame toxicity is more related to the GSH system. In addition, the results suggest an anxiolytic effect of NAC in animals treated with aspartame. NAC was able to restore most of the changes in the GSH-related system in brain regions after long-term ingestion of aspartame.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESO aspartame é um edulcorante sintético amplamente utilizado por indivíduos com dietas de restrição de sacarose, glicose ou frutose ou por aqueles que buscam a perda de peso. Muitos estudos têm indicado que seu uso está relacionado com alterações a nível do sistema nervoso central, bem como com a indução de estresse oxidativo. No entanto, os mecanismos responsáveis para tais efeitos não estão totalmente esclarecidos, bem como o potencial de compostos antioxidantes, tais como a N-acetilcisteína, em amenizar esses danos. Assim, este estudo avaliou os efeitos da N-acetilcisteína (NAC) (163 mg/kg, i.p.) sobre parâmetros comportamentais e oxidativos frente a administração a longo prazo (90 dias) de aspartame (80 mg/kg, v.o.) em regiões cerebrais de camundongos. Para tanto, camundongos Swiss albinos machos foram divididos em três grupos: controle – receberam ambos veículos, o do aspartame e o da N-acetilcisteína; ASP – receberam o aspartame, e o veículo da N-acetilcisteína; e ASPNAC – receberam ambos tratamentos, aspartame e N-acetilcisteína. O aspartame foi administrado durante 90 dias, enquanto a NAC foi injetada apenas nos últimos 30 dias. Na última semana do período experimental, os animais tiveram seu comportamento avaliado através do teste de campo aberto. Ao fim dos 90 dias, os animais foram anestesiados e eutanasiados para a remoção do encéfalo e separação das seguintes regiões: córtex cerebral, hipocampo e cerebelo, nas quais foi realizada a pesquisa por biomarcadores de estresse oxidativo e a expressão gênica da subunidade catalítica da glutamato cisteína ligase (Gclc), da cistationina γ-liase (Cth) e da tiorredoxina 1 (Trx1). Os resultados obtidos demonstraram que os camundongos tratados com aspartame e NAC apresentaram uma diminuição no número de crossings e um aumento no tempo gasto na área central em relação aos animais do controle e tratados somente com aspartame. Apesar de não ter alterado o sistema da tioredoxina, a administração de aspartame causou uma severa depleção nos níveis de tiois não proteicos, assim como na atividade da glutationa peroxidase. Ambas alterações foram restauradas pelo tratamento com a NAC. O aspartame também desencadeou uma diminuição nos níveis de mRNA da Gclc e da Cth e o tratamento com a NAC restaurou os níveis de Gclc. Conclui-se a partir destes resultados que, apesar de não ter alterado o sistema da tiorredoxina, o tratamento com aspartame causou uma severa depleção dos níveis de GSH, o que pode ser devido a diminuição dos níveis de mRNA da Gclc e da Cth, demonstrando que o mecanismo de ação da toxicidade do aspartame está mais relacionado ao sistema da GSH. Além disso, os resultados sugerem um efeito ansiolítico da NAC em animais tratados com aspartame. A NAC foi capaz de restaurar a maioria das alterações no sistema relacionado a GSH em regiões cerebrais após a ingestão a longo prazo de aspartame.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdePavanato, Maria Amáliahttp://lattes.cnpq.br/8701892865724171Machado, Alencar Kolinskihttp://lattes.cnpq.br/7339960872140748Bochi, Guilherme Vargashttp://lattes.cnpq.br/4191221572795869Bressan, Caroline Azzolin2021-03-18T11:18:11Z2021-03-18T11:18:11Z2018-01-31info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/20451porAttribution-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:UFSM2021-03-19T06:01:29Zoai:repositorio.ufsm.br:1/20451Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2021-03-19T06:01:29Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame N-acetylcysteine evaluation on behavioral and oxidative parameters front long term administration of aspartame |
title |
Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame |
spellingShingle |
Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame Bressan, Caroline Azzolin Glutationa Adoçantes de baixa caloria Tiorredoxina Regiões cerebrais Glutathione Low-calorie sweeteners Tioredoxin Brain regions CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame |
title_full |
Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame |
title_fullStr |
Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame |
title_full_unstemmed |
Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame |
title_sort |
Avaliação da N-acetilcisteína sobre os parâmetros comportamentais e oxidativos frente à administração a longo prazo de aspartame |
author |
Bressan, Caroline Azzolin |
author_facet |
Bressan, Caroline Azzolin |
author_role |
author |
dc.contributor.none.fl_str_mv |
Pavanato, Maria Amália http://lattes.cnpq.br/8701892865724171 Machado, Alencar Kolinski http://lattes.cnpq.br/7339960872140748 Bochi, Guilherme Vargas http://lattes.cnpq.br/4191221572795869 |
dc.contributor.author.fl_str_mv |
Bressan, Caroline Azzolin |
dc.subject.por.fl_str_mv |
Glutationa Adoçantes de baixa caloria Tiorredoxina Regiões cerebrais Glutathione Low-calorie sweeteners Tioredoxin Brain regions CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Glutationa Adoçantes de baixa caloria Tiorredoxina Regiões cerebrais Glutathione Low-calorie sweeteners Tioredoxin Brain regions CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Aspartame is a synthetic sweetener widely used by individuals with restriction diets of sucrose, glucose or fructose or by those seeking wight loss. Several studies have indicated that its use is related to changes in the central nervous system, as well as to the induction of oxidative stress. However, the mechanisms responsible for such effects are not fully understood, as well as the potential of antioxidant compounds, such as N-acetylcysteine, in mitigating such damages. Thus, this study evaluated the effects of N-acetylcysteine (NAC) (163 mg/kg, i.p) on behavioral and oxidative parameters against the long-term (90 days) administration of aspartame (80 mg/kg, v.o) in brain regions of mice. For this purpose, Swiss albino male mice were divided in three groups: control – received both aspartame and Nacetylcysteine vehicles; ASP – received aspartame, and the N-acetylcysteine vehicle; and ASP-NAC – received both treatments, aspartame and N-acetylcysteine. Aspartame was administered for 90 days, while NAC was injected only in the last 30 days. In the last week of the experimental period, the animals had their behavior evaluated through the open field test. At the end of the 90 days, the animals were anesthetized and euthanized for the removal of the brain and separation of the following regions: cerebral cortex, hippocampus and cerebellum, in which was held the research of the oxidative stress biomarkers and the gene expression of catalytic subunit of glutamate cysteine ligase (Gclc), cystathionin γ-lyase (Cth) and thioredoxin 1 (Trx1). The results showed that the mice treated with aspartame and NAC presented a decrease in the number of crossings and an increase in the time spent in the central area in relation to the control animals and treated with aspartame alone. Although it did not alter the thioredoxin system, the administration of aspartame caused severe depletion in non-protein thiois (NPSH) levels as well as glutathione peroxidase (GPx) activity. Both changes were restored by treatment with NAC. Aspartame also triggered a decrease in Gclc and Cth mRNA levels. Treatment with NAC restored Gclc levels. It is concluded from these results that, although it did not alter the thioredoxin system, treatment with aspartame caused a severe depletion of NPSH levels, which may be due to the decrease in Gclc and Cth mRNA levels, demonstrating that the mechanism of action of aspartame toxicity is more related to the GSH system. In addition, the results suggest an anxiolytic effect of NAC in animals treated with aspartame. NAC was able to restore most of the changes in the GSH-related system in brain regions after long-term ingestion of aspartame. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-01-31 2021-03-18T11:18:11Z 2021-03-18T11:18:11Z |
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/1/20451 |
url |
http://repositorio.ufsm.br/handle/1/20451 |
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 Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmacologia UFSM Programa de Pós-Graduação em Farmacologia Centro de Ciências da Saúde |
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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1805922014383308800 |