Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame

Detalhes bibliográficos
Autor(a) principal: Brener, Carlos Eduardo de Souza
Data de Publicação: 2017
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Manancial - Repositório Digital da UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/18230
Resumo: Currently, many diabetic, obese, and/or those seeking a healthier lifestyle are looking for foods with a sweet taste, but without the addition of energy, preferring to use sweeteners such as aspartame (ASP). The ASP is widely distributed in products available in the market, especially in those that lack sucrose, and its consumption has been approved for more than 20 years by the FDA (Food and Drug Administration). However, there are concerns and evidences that suggest possible adverse effects of ASP metabolites, resulting in alterations in the antioxidant defense system, especially due to the depletion of glutathione levels (GSH) and the activity of the enzymes dependent on it, causing oxidative damages. Considering that obese and/or diabetic individuals replace the use of sucrose by artificial sweeteners, such as ASP, which produces metabolites capable of causing possible adverse effects, it is of fundamental interest to use antioxidant compounds that reduce the harmful effects caused by the sweetener, which are capable of protecting cellular constituents. Thus, N-acetylcysteine (NAC), an excellent antioxidant, has been shown to be effective in restoring the levels of GSH and enzymes related to its metabolism. Thus, the objective of this work was to evaluate the effect of N-acetylcysteine on biochemical and oxidative parameters in renal tissue of mice receiving chronic oral administration of aspartame. For this, mice (n = 30) were divided into three groups: Control, treated with ASP (80 mg.kg-1, vol) and treated with ASP and NAC (163 mg.kg-1, intraperitoneally), during 90 days. From the 60th day of treatment, the animals of the ASP-NAC group started receiving the dose of 163 mg.kg-1. After the experimental period, the animals were euthanized and their kidneys removed for further analysis. Levene’s test was used to verify whether the data were parametric. Two-way analysis of variance followed by Tukey’s test was performed to assess the differences among the groups. The data of this work showed absence of significant difference between groups studied in the content of substances that react to thiobarbituric acid and carbonyl proteins, indicating that there was no damage in the lipids and proteins in the treatment with ASP in mice. Myeloperoxidase activity (MPO) was similar in the ASP group and in the animals treated with ASP-NAC when compared to the control group. The present study showed that oral administration of ASP (80 mg.kg-1) leads to a significant decrease in CAT activity in renal tissue. There is also a decrease in the content of non-protein thiols in animals treated with ASP. The activity of glutathione-related enzymes such as glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) showed a decrease in the ASP group, as does the enzyme thioredoxin reductase (TrxR). The NAC treatment reversed the activity of the CAT, GPx, GST, GR and TrxR enzymes, showing that this drug is a potential in the treatment of disorders caused by oxidative stress.
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spelling Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartameEffect of N-acetylcysteine on the glutathione system in kidney of mice under chronic aspartame administrationAspartameGlutationaN-acetilcisteínaRimGlutathioneN-acetylcysteineKidneyCNPQ::CIENCIAS DA SAUDE::FARMACIACurrently, many diabetic, obese, and/or those seeking a healthier lifestyle are looking for foods with a sweet taste, but without the addition of energy, preferring to use sweeteners such as aspartame (ASP). The ASP is widely distributed in products available in the market, especially in those that lack sucrose, and its consumption has been approved for more than 20 years by the FDA (Food and Drug Administration). However, there are concerns and evidences that suggest possible adverse effects of ASP metabolites, resulting in alterations in the antioxidant defense system, especially due to the depletion of glutathione levels (GSH) and the activity of the enzymes dependent on it, causing oxidative damages. Considering that obese and/or diabetic individuals replace the use of sucrose by artificial sweeteners, such as ASP, which produces metabolites capable of causing possible adverse effects, it is of fundamental interest to use antioxidant compounds that reduce the harmful effects caused by the sweetener, which are capable of protecting cellular constituents. Thus, N-acetylcysteine (NAC), an excellent antioxidant, has been shown to be effective in restoring the levels of GSH and enzymes related to its metabolism. Thus, the objective of this work was to evaluate the effect of N-acetylcysteine on biochemical and oxidative parameters in renal tissue of mice receiving chronic oral administration of aspartame. For this, mice (n = 30) were divided into three groups: Control, treated with ASP (80 mg.kg-1, vol) and treated with ASP and NAC (163 mg.kg-1, intraperitoneally), during 90 days. From the 60th day of treatment, the animals of the ASP-NAC group started receiving the dose of 163 mg.kg-1. After the experimental period, the animals were euthanized and their kidneys removed for further analysis. Levene’s test was used to verify whether the data were parametric. Two-way analysis of variance followed by Tukey’s test was performed to assess the differences among the groups. The data of this work showed absence of significant difference between groups studied in the content of substances that react to thiobarbituric acid and carbonyl proteins, indicating that there was no damage in the lipids and proteins in the treatment with ASP in mice. Myeloperoxidase activity (MPO) was similar in the ASP group and in the animals treated with ASP-NAC when compared to the control group. The present study showed that oral administration of ASP (80 mg.kg-1) leads to a significant decrease in CAT activity in renal tissue. There is also a decrease in the content of non-protein thiols in animals treated with ASP. The activity of glutathione-related enzymes such as glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) showed a decrease in the ASP group, as does the enzyme thioredoxin reductase (TrxR). The NAC treatment reversed the activity of the CAT, GPx, GST, GR and TrxR enzymes, showing that this drug is a potential in the treatment of disorders caused by oxidative stress.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESAtualmente, muitos indivíduos diabéticos, obesos e/ou aqueles que procuram um estilo de vida mais saudável buscam alimentos com o sabor doce, mas sem a adição de energia, preferindo utilizar adoçantes, como o aspartame (ASP). O ASP encontra-se amplamente distribuído em produtos disponíveis no mercado, especialmente naqueles que apresentam ausência de sacarose, e seu consumo está aprovado há mais de 20 anos pela FDA (Food and Drug Administration). No entanto, existem preocupações e evidências que sugerem possíveis efeitos adversos dos metabólitos do ASP, resultando inclusive em alterações no sistema de defesa antioxidante, especialmente, em decorrência da depleção dos níveis de glutationa (GSH) e da atividade das enzimas dependentes dela, podendo ocasionar danos oxidativos. Considerando que os indivíduos obesos e/ou diabéticos substituem o uso da sacarose por adoçantes artificiais, como o ASP, o qual produz metabólitos capazes de causar possíveis efeitos adversos, é de fundamental interesse a utilização de compostos antioxidantes que reduzam os efeitos lesivos causados por esse adoçante, os quais sejam capazes de proteger os constituintes celulares. Assim, destaca-se a N-acetilcisteína (NAC), um excelente antioxidante que demonstrou ser efetivo ao restabelecer os níveis de GSH e das enzimas relacionadas ao seu metabolismo. Dessa forma, o objetivo deste trabalho foi avaliar o efeito da N- acetilcisteína sobre os parâmetros bioquímicos e oxidativos em tecido renal de camundongos que receberam administração oral crônica de aspartame. Para isso, foram utilizados camundongos (n = 30), divididos em três grupos: Controle, tratado com ASP (80 mg.kg-1, v.o.) e tratado com ASP e NAC (163 mg.kg-1, intraperitoneal), durante 90 dias. A partir do 60º dia de tratamento, os animais do grupo ASP-NAC começaram a receber a dose de 163 mg.kg-1. Após o período experimental, os animais foram eutanasiados e seus rins removidos para as análises posteriores. O teste de Levene foi utilizado para verificar se os dados são paramétricos. Realizou-se a análise de variância de duas vias seguida pelo teste de Tukey para avaliar as diferenças entre os grupos. Os dados deste trabalho mostraram ausência de diferença significativa entre grupos estudados no conteúdo de substâncias que reagem ao ácido tiobarbitúrico e proteínas carbonil, indicando que não houve danos nos lipídios e proteínas no tratamento com ASP em camundongos. A atividade da mieloperoxidase (MPO) foi semelhante no grupo ASP e nos animais tratados com ASP-NAC quando comparados ao grupo controle. O presente estudo mostrou que a administração oral de ASP (80 mg.kg-1) leva a uma significativa diminuição na atividade da CAT no tecido renal. Há também uma diminuição do conteúdo de tióis não proteicos nos animais tratados com ASP. A atividade de enzimas relacionadas à glutationa como a glutationa peroxidase (GPx), glutationa S- transferase (GST) e glutationa redutase (GR) mostrou uma diminuição no grupo ASP, assim como o que acontece com a enzima tiorredoxina redutase (TrxR). O tratamento com NAC reverteu a atividade das enzimas CAT, GPx, GST, GR e TrxR, mostrando que este fármaco é um potencial no tratamento de distúrbios causados pelo estresse oxidativo.Universidade Federal de Santa MariaBrasilFarmacologiaUFSMPrograma de Pós-Graduação em FarmacologiaCentro de Ciências da SaúdePavanato, Maria Amáliahttp://lattes.cnpq.br/8701892865724171Bauermann, Liliane de Freitashttp://lattes.cnpq.br/5849925846135968Marroni, Norma Anair Possahttp://lattes.cnpq.br/0504456375208670Brener, Carlos Eduardo de Souza2019-09-16T17:20:44Z2019-09-16T17:20:44Z2017-03-24info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/18230porAttribution-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:UFSM2019-09-17T06:01:30Zoai:repositorio.ufsm.br:1/18230Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-09-17T06:01:30Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false
dc.title.none.fl_str_mv Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame
Effect of N-acetylcysteine on the glutathione system in kidney of mice under chronic aspartame administration
title Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame
spellingShingle Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame
Brener, Carlos Eduardo de Souza
Aspartame
Glutationa
N-acetilcisteína
Rim
Glutathione
N-acetylcysteine
Kidney
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame
title_full Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame
title_fullStr Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame
title_full_unstemmed Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame
title_sort Efeito da N-acetilcisteína no sistema da glutationa em rim de camundongos sob administração crônica de aspartame
author Brener, Carlos Eduardo de Souza
author_facet Brener, Carlos Eduardo de Souza
author_role author
dc.contributor.none.fl_str_mv Pavanato, Maria Amália
http://lattes.cnpq.br/8701892865724171
Bauermann, Liliane de Freitas
http://lattes.cnpq.br/5849925846135968
Marroni, Norma Anair Possa
http://lattes.cnpq.br/0504456375208670
dc.contributor.author.fl_str_mv Brener, Carlos Eduardo de Souza
dc.subject.por.fl_str_mv Aspartame
Glutationa
N-acetilcisteína
Rim
Glutathione
N-acetylcysteine
Kidney
CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic Aspartame
Glutationa
N-acetilcisteína
Rim
Glutathione
N-acetylcysteine
Kidney
CNPQ::CIENCIAS DA SAUDE::FARMACIA
description Currently, many diabetic, obese, and/or those seeking a healthier lifestyle are looking for foods with a sweet taste, but without the addition of energy, preferring to use sweeteners such as aspartame (ASP). The ASP is widely distributed in products available in the market, especially in those that lack sucrose, and its consumption has been approved for more than 20 years by the FDA (Food and Drug Administration). However, there are concerns and evidences that suggest possible adverse effects of ASP metabolites, resulting in alterations in the antioxidant defense system, especially due to the depletion of glutathione levels (GSH) and the activity of the enzymes dependent on it, causing oxidative damages. Considering that obese and/or diabetic individuals replace the use of sucrose by artificial sweeteners, such as ASP, which produces metabolites capable of causing possible adverse effects, it is of fundamental interest to use antioxidant compounds that reduce the harmful effects caused by the sweetener, which are capable of protecting cellular constituents. Thus, N-acetylcysteine (NAC), an excellent antioxidant, has been shown to be effective in restoring the levels of GSH and enzymes related to its metabolism. Thus, the objective of this work was to evaluate the effect of N-acetylcysteine on biochemical and oxidative parameters in renal tissue of mice receiving chronic oral administration of aspartame. For this, mice (n = 30) were divided into three groups: Control, treated with ASP (80 mg.kg-1, vol) and treated with ASP and NAC (163 mg.kg-1, intraperitoneally), during 90 days. From the 60th day of treatment, the animals of the ASP-NAC group started receiving the dose of 163 mg.kg-1. After the experimental period, the animals were euthanized and their kidneys removed for further analysis. Levene’s test was used to verify whether the data were parametric. Two-way analysis of variance followed by Tukey’s test was performed to assess the differences among the groups. The data of this work showed absence of significant difference between groups studied in the content of substances that react to thiobarbituric acid and carbonyl proteins, indicating that there was no damage in the lipids and proteins in the treatment with ASP in mice. Myeloperoxidase activity (MPO) was similar in the ASP group and in the animals treated with ASP-NAC when compared to the control group. The present study showed that oral administration of ASP (80 mg.kg-1) leads to a significant decrease in CAT activity in renal tissue. There is also a decrease in the content of non-protein thiols in animals treated with ASP. The activity of glutathione-related enzymes such as glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR) showed a decrease in the ASP group, as does the enzyme thioredoxin reductase (TrxR). The NAC treatment reversed the activity of the CAT, GPx, GST, GR and TrxR enzymes, showing that this drug is a potential in the treatment of disorders caused by oxidative stress.
publishDate 2017
dc.date.none.fl_str_mv 2017-03-24
2019-09-16T17:20:44Z
2019-09-16T17:20:44Z
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/1/18230
url http://repositorio.ufsm.br/handle/1/18230
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)
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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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