Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/20483 |
Resumo: | Studies have been demonstrating an increasing number of secondary complications caused by diabetes. Among them are neuropsychiatric diseases such as anxiety and depression. In addition, oxidative stress is known to play a key role in this metabolic disorder. Thus, compounds that have antioxidant activity have been considered as possible therapeutic agents in hyperglycemia models. In this context, we highlight diphenyl diselenide (DD), an organocalcogen with several pharmacological activities, including antioxidant and anxiolytic. In the present work, using zebrafish as a model organism, we investigated the effects of diet containing DD on behavioral, biochemical and molecular parameters in a model of hyperglycemia. Initially, in order to evaluate a possible toxicity of the compound, the fish were supplemented for 74 days with food containing 3 different concentrations of the compound (1, 2 and 3 mg / kg). After the 74 days, mortality rate analyzes as well as locomotor and anxiety-like behavior parameters (through the "light-dark" test and the "novel tank") did not show any alteration caused by supplementation. Therefore, we used the concentration of 3mg / kg in the hyperglycemia model. The animals were supplemented with diphenyl diselenide for 60 days. Then, they were exposed for 14 days to a solution of 111 mM glucose, remaining with the supplementation in that period. After that, blood glucose measurements, behavioral tests as well as biochemical and molecular analyzes were performed on the animals' brains. The glycemia of the animals exposed to glucose was increased around 3.5 times and supplementation with DD was able to partially reduce this increase. Through the "light-dark" test and the "novel tank" test, an increase in the anxiety-like behavior of animals exposed to glucose was observed. However, this effect was not observed in animals supplemented with DD. In order to understand possible mechanisms involved in the hypoglycemic effect as well as in the neuroprotection caused by DD, biochemical and molecular assays were performed in the fish’s brain. DD supplementation was able to prevent glucose-induced decrease in insulin receptor expression (Insra1, Insra2, Insrb1, Insrb2) in addition to increasing the expression of glucose transporter 3 (GLUT3). In the oxidative stress parameters, the diet containing DD partially prevented the decrease of the SOD enzyme activity caused by exposure to glucose and had an effect per se increasing the activity of the GPx and GST enzymes and the NPSH levels. In addition, DD supplementation was able to prevent the decrease caused by exposure to glucose in the expression of GPx3A and the transcription factor Nrf2. Finally, we evaluated lipid oxidation parameters (through the measurement of thiobarbituric acid reactive substances (TBARS)) and protein oxidation (through the levels of carbonylated preoteins (CP)). The results showed that both parameters were significantly increased by exposure to glucose and that the diet containing DD was effective in preventing this increase. The results of this work highlight the promising role of DD, in addition to showing for the first time possible mechanisms related to its hypoglycemic and neuroprotective effect. |
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2021-04-05T19:09:27Z2021-04-05T19:09:27Z2018-08-06http://repositorio.ufsm.br/handle/1/20483Studies have been demonstrating an increasing number of secondary complications caused by diabetes. Among them are neuropsychiatric diseases such as anxiety and depression. In addition, oxidative stress is known to play a key role in this metabolic disorder. Thus, compounds that have antioxidant activity have been considered as possible therapeutic agents in hyperglycemia models. In this context, we highlight diphenyl diselenide (DD), an organocalcogen with several pharmacological activities, including antioxidant and anxiolytic. In the present work, using zebrafish as a model organism, we investigated the effects of diet containing DD on behavioral, biochemical and molecular parameters in a model of hyperglycemia. Initially, in order to evaluate a possible toxicity of the compound, the fish were supplemented for 74 days with food containing 3 different concentrations of the compound (1, 2 and 3 mg / kg). After the 74 days, mortality rate analyzes as well as locomotor and anxiety-like behavior parameters (through the "light-dark" test and the "novel tank") did not show any alteration caused by supplementation. Therefore, we used the concentration of 3mg / kg in the hyperglycemia model. The animals were supplemented with diphenyl diselenide for 60 days. Then, they were exposed for 14 days to a solution of 111 mM glucose, remaining with the supplementation in that period. After that, blood glucose measurements, behavioral tests as well as biochemical and molecular analyzes were performed on the animals' brains. The glycemia of the animals exposed to glucose was increased around 3.5 times and supplementation with DD was able to partially reduce this increase. Through the "light-dark" test and the "novel tank" test, an increase in the anxiety-like behavior of animals exposed to glucose was observed. However, this effect was not observed in animals supplemented with DD. In order to understand possible mechanisms involved in the hypoglycemic effect as well as in the neuroprotection caused by DD, biochemical and molecular assays were performed in the fish’s brain. DD supplementation was able to prevent glucose-induced decrease in insulin receptor expression (Insra1, Insra2, Insrb1, Insrb2) in addition to increasing the expression of glucose transporter 3 (GLUT3). In the oxidative stress parameters, the diet containing DD partially prevented the decrease of the SOD enzyme activity caused by exposure to glucose and had an effect per se increasing the activity of the GPx and GST enzymes and the NPSH levels. In addition, DD supplementation was able to prevent the decrease caused by exposure to glucose in the expression of GPx3A and the transcription factor Nrf2. Finally, we evaluated lipid oxidation parameters (through the measurement of thiobarbituric acid reactive substances (TBARS)) and protein oxidation (through the levels of carbonylated preoteins (CP)). The results showed that both parameters were significantly increased by exposure to glucose and that the diet containing DD was effective in preventing this increase. The results of this work highlight the promising role of DD, in addition to showing for the first time possible mechanisms related to its hypoglycemic and neuroprotective effect.Estudos vêm demonstrando um número cada vez maior de complicações secundárias causadas pelo diabetes. Dentre elas, estão doenças neuropsiquiátricas como ansiedade e depressão. Além disso, sabe-se que o estresse oxidativo desempenha um papel chave nessa desordem metabólica. Dessa forma, compostos que possuem atividade antioxidante vêm sendo considerados como possíveis agentes terapêuticos em modelos de hiperglicemia. Nesse contexto, destacamos o disseleneto de difenila (DD), um organocalcogênio com diversas atividades farmacológicas, incluindo antioxidante e neuroprotetora. No presente trabalho, utilizando o peixe-zebra como organismo modelo, investigamos os efeitos de uma dieta contendo DD sobre parâmetros comportamentais, bioquímicos e moleculares em um modelo de hiperglicemia. Inicialmente, com o intuito de avaliar uma possível toxicidade do composto, os peixes foram suplementados durante 74 dias com ração contendo 3 diferentes concentrações do composto (1, 2 e 3 mg/Kg). Nenhuma das concentrações utilizadas afetou a taxa de sobrevivência bem como parâmetros locomotores e de comportamento tipo ansiedade (através do teste “claro-escuro” e “tanque novo”). Sendo assim, escolhemos a concentração de 3mg/Kg para ser usada no modelo de hiperglicemia. Os animais receberam a suplementação com disseleneto de difenila por 74 dias. Durante os últimos 14 dias, os animais foram concomitantemente expostos a uma solução de 111 mM de glicose. Após, foram realizadas medidas da glicemia, testes comportamentais bem como análises bioquímicas e moleculares usando o cérebro como tecido alvo. A glicemia dos animais expostos à glicose foi aumentada em torno de 3,5 vezes e a suplementação com DD reduziu parcialmente esse aumento. Através do teste do “claro-escuro” e do “tanque novo” foi possível observar um aumento no comportamento tipo ansiedade dos animais expostos à glicose. Esse comportamento não foi observado nos animais suplementados com DD. Afim de entender os possíveis mecanismos envolvidos no efeito hipoglicêmico bem como na neuroproteção causada pelo DD, ensaios bioquímicos e moleculares foram realizados no cérebro dos peixes. A exposição a glicose causou uma diminuição na expressão dos receptores de insulina (Insra1, Insra2, Insrb1, Insrb2), a qual foi normalizada aos níveis do controle pelo DD. Além disso, DD per se aumentou a expressão do tranportador de glicose 3 (GLUT3). Nos parâmetros de estresse oxidativo, observamos que a exposição à glicose causou aumento nos níveis de peroxidação lipídica (avaliada através da medida de substancias reativas ao ácido tiobarbitúrico (TBARS)) e oxidação de proteínas no tecido cerebral (avaliada através dos níveis de preoteínas carboniladas (CP) e alteração na atividade da enzima superóxido dismutase (SOD). Esses efeitos foram prevenidos pelo tratamento com DD. A suplementação aumentou per se a atividade das enzimas GPx e GST e os níveis de NPSH. Em paralelo, a suplementação com DD normalizou as alterações observadas nos níveis de expressão dos mRNA relativos ao fator de transcrição Nrf2 e a enzima GPx3A. Os resultados obtidos mostram a eficácia da dieta em melhorar alterações bioquímicas e comportamentais induzidas por hiperglicemia, indentificando e pontuando a participação da sinalização redox e da via da insulina nos mecanismos subjascentes ao efeito hipoglicemiante e neuroprotetor do DD.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESporUniversidade 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/openAccessDiabetesHiperglicemiaDisseleneto de difenilaAnsiedadeEstresse oxidativoPeixe-zebraHyperglycaemiaDiphenyl diselenideAnxietyOxidative stressZebrafishCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEfeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebraEffects of the diet containing diphenyl diselenide on behavioral, biochemical and molecular responses in a hyperglycemia model in zebrafishinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisBarbosa, Nilda Berenice de Vargashttp://lattes.cnpq.br/5901511067144019Rico, Eduardo PachecoSoares, Félix Alexandre AntunesFranco, Jeferson LuisFolmer, Vanderleihttp://lattes.cnpq.br/0409790717340977Santos, Matheus Mülling dos20080000000260060060060060087b11d6d-46b4-49bc-b979-5342a4cd48ff570f18fc-5a49-4927-9017-969f29ef775f67be83fd-7da5-4987-af79-2c1ffeab8156161311d0-e9c6-4e08-a436-85b4822199b41133a5ad-51c6-405e-b37c-56e2810aafb69363483b-d41c-4214-92f2-2e2c8d2506c2reponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALTES_PPGCBBT_2018_SANTOS_MATHEUS.pdfTES_PPGCBBT_2018_SANTOS_MATHEUS.pdfTeseapplication/pdf12511481http://repositorio.ufsm.br/bitstream/1/20483/1/TES_PPGCBBT_2018_SANTOS_MATHEUS.pdf3549a9df33c75c661b65928bd589c1c0MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv |
Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra |
dc.title.alternative.eng.fl_str_mv |
Effects of the diet containing diphenyl diselenide on behavioral, biochemical and molecular responses in a hyperglycemia model in zebrafish |
title |
Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra |
spellingShingle |
Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra Santos, Matheus Mülling dos Diabetes Hiperglicemia Disseleneto de difenila Ansiedade Estresse oxidativo Peixe-zebra Hyperglycaemia Diphenyl diselenide Anxiety Oxidative stress Zebrafish CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra |
title_full |
Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra |
title_fullStr |
Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra |
title_full_unstemmed |
Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra |
title_sort |
Efeitos da dieta contendo disseleneto de difenila sobre respostas comportamentais, bioquímicas e moleculares em um modelo de hiperglicemia em peixe-zebra |
author |
Santos, Matheus Mülling dos |
author_facet |
Santos, Matheus Mülling dos |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Barbosa, Nilda Berenice de Vargas |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5901511067144019 |
dc.contributor.referee1.fl_str_mv |
Rico, Eduardo Pacheco |
dc.contributor.referee2.fl_str_mv |
Soares, Félix Alexandre Antunes |
dc.contributor.referee3.fl_str_mv |
Franco, Jeferson Luis |
dc.contributor.referee4.fl_str_mv |
Folmer, Vanderlei |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/0409790717340977 |
dc.contributor.author.fl_str_mv |
Santos, Matheus Mülling dos |
contributor_str_mv |
Barbosa, Nilda Berenice de Vargas Rico, Eduardo Pacheco Soares, Félix Alexandre Antunes Franco, Jeferson Luis Folmer, Vanderlei |
dc.subject.por.fl_str_mv |
Diabetes Hiperglicemia Disseleneto de difenila Ansiedade Estresse oxidativo Peixe-zebra |
topic |
Diabetes Hiperglicemia Disseleneto de difenila Ansiedade Estresse oxidativo Peixe-zebra Hyperglycaemia Diphenyl diselenide Anxiety Oxidative stress Zebrafish CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Hyperglycaemia Diphenyl diselenide Anxiety Oxidative stress Zebrafish |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Studies have been demonstrating an increasing number of secondary complications caused by diabetes. Among them are neuropsychiatric diseases such as anxiety and depression. In addition, oxidative stress is known to play a key role in this metabolic disorder. Thus, compounds that have antioxidant activity have been considered as possible therapeutic agents in hyperglycemia models. In this context, we highlight diphenyl diselenide (DD), an organocalcogen with several pharmacological activities, including antioxidant and anxiolytic. In the present work, using zebrafish as a model organism, we investigated the effects of diet containing DD on behavioral, biochemical and molecular parameters in a model of hyperglycemia. Initially, in order to evaluate a possible toxicity of the compound, the fish were supplemented for 74 days with food containing 3 different concentrations of the compound (1, 2 and 3 mg / kg). After the 74 days, mortality rate analyzes as well as locomotor and anxiety-like behavior parameters (through the "light-dark" test and the "novel tank") did not show any alteration caused by supplementation. Therefore, we used the concentration of 3mg / kg in the hyperglycemia model. The animals were supplemented with diphenyl diselenide for 60 days. Then, they were exposed for 14 days to a solution of 111 mM glucose, remaining with the supplementation in that period. After that, blood glucose measurements, behavioral tests as well as biochemical and molecular analyzes were performed on the animals' brains. The glycemia of the animals exposed to glucose was increased around 3.5 times and supplementation with DD was able to partially reduce this increase. Through the "light-dark" test and the "novel tank" test, an increase in the anxiety-like behavior of animals exposed to glucose was observed. However, this effect was not observed in animals supplemented with DD. In order to understand possible mechanisms involved in the hypoglycemic effect as well as in the neuroprotection caused by DD, biochemical and molecular assays were performed in the fish’s brain. DD supplementation was able to prevent glucose-induced decrease in insulin receptor expression (Insra1, Insra2, Insrb1, Insrb2) in addition to increasing the expression of glucose transporter 3 (GLUT3). In the oxidative stress parameters, the diet containing DD partially prevented the decrease of the SOD enzyme activity caused by exposure to glucose and had an effect per se increasing the activity of the GPx and GST enzymes and the NPSH levels. In addition, DD supplementation was able to prevent the decrease caused by exposure to glucose in the expression of GPx3A and the transcription factor Nrf2. Finally, we evaluated lipid oxidation parameters (through the measurement of thiobarbituric acid reactive substances (TBARS)) and protein oxidation (through the levels of carbonylated preoteins (CP)). The results showed that both parameters were significantly increased by exposure to glucose and that the diet containing DD was effective in preventing this increase. The results of this work highlight the promising role of DD, in addition to showing for the first time possible mechanisms related to its hypoglycemic and neuroprotective effect. |
publishDate |
2018 |
dc.date.issued.fl_str_mv |
2018-08-06 |
dc.date.accessioned.fl_str_mv |
2021-04-05T19:09:27Z |
dc.date.available.fl_str_mv |
2021-04-05T19:09:27Z |
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/1/20483 |
url |
http://repositorio.ufsm.br/handle/1/20483 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.cnpq.fl_str_mv |
200800000002 |
dc.relation.confidence.fl_str_mv |
600 600 600 600 600 |
dc.relation.authority.fl_str_mv |
87b11d6d-46b4-49bc-b979-5342a4cd48ff 570f18fc-5a49-4927-9017-969f29ef775f 67be83fd-7da5-4987-af79-2c1ffeab8156 161311d0-e9c6-4e08-a436-85b4822199b4 1133a5ad-51c6-405e-b37c-56e2810aafb6 9363483b-d41c-4214-92f2-2e2c8d2506c2 |
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:Biblioteca Digital de Teses e Dissertações do UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
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Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
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UFSM |
reponame_str |
Biblioteca Digital de Teses e Dissertações do UFSM |
collection |
Biblioteca Digital de Teses e Dissertações do UFSM |
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repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1801485204549795840 |