Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/18425 |
Resumo: | The obesity epidemic is a worldwide public health problem and is considered one of the leading causes of death and disability worldwide. This is because the pathophysiology of this disease is extremely complex and involves a series of events in cascades that can even evolve into irreversible damage. Regarding treatment, drugs currently available for the treatment of obesity are often inefficient and have adverse effects, so the search for new drugs for the treatment of metabolic diseases has been growing so much in recent years. In this context, organic compounds of selenium have been studied in the last decades, mainly due to their diverse pharmacological activities, among them, antioxidant, neuroprotective, anticancer, antiviral, immunosuppressive, antimicrobial, anxiolytic, antidepressant-like and anti-inflammatory. However, these compounds have recently attracted attention because of their beneficial effects on the regulation of metabolic homeostasis. The present thesis aimed to investigate the pharmacological effects of 4,4'-dichloro-diphenyl diselenide, (p-ClPhSe)2 in hyperglycemia and obesity models induced by the administration of fructose or monosodium glutamate (MSG) in rats. In the manuscript 1, an insulin-mimetic effect of (p-ClPhSe)2 was demonstrated in vitro; this compound stimulated the glucose uptake into skeletal muscle and its acute antihyperglycemic effect in a model of hyperglycemia induced by the administration of fructose in rats. Furthermore, in the manuscript 1, acute treatment with (p-ClPhSe)2 protected against liver metabolic alterations induced by fructose; this compound redirected the carbohydrate metabolism. In that sense, in the article 1, a homeostatic effect of subchronic treatment with (p-ClPhSe)2 was demonstrated, this compound reduced the first signs of obesity induced with the administration of GMS in rats. Whereas in the manuscript 2, it was possible to observe a hepatoprotective effect of subchronic treatment with (p-ClPhSe)2 against the mitochondrial dysfunction, oxidative stress and inflammation induced by the administration of GMS in rats. In addition, a beneficial effect of subchronic treatment with (p-ClPhSe)2 against metabolic dysfunction in blood, liver and skeletal muscle induced by the administration of GMS in rats was demonstrated in manuscript 3. Taken together, the present results demonstrated that the compound, (p-ClPhSe)2, has several pharmacological properties, such as antihyperglycemic, insulin-mimetic, anti-inflammatory and antioxidant. It is known that drugs used for the treatment of obesity are often inefficient due to the complications present during the progression of obesity. Considering the pharmacological effects of (p-ClPhSe)2 demonstrated in the present study, this organic compound of selenium may be a future therapeutic alternative for the treatment of this pathology and its complications. |
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Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratosPharmacological action of 4,4'-dichloro-diphenyl diselenide in rat hyperglycemia and obesity modelsSelênioObesidadeAlterações metabólicasInflamaçãoEstresse oxidativoSeleniumObesityMetabolic alterationsInflammationOxidative stressInsulin-mimeticCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAThe obesity epidemic is a worldwide public health problem and is considered one of the leading causes of death and disability worldwide. This is because the pathophysiology of this disease is extremely complex and involves a series of events in cascades that can even evolve into irreversible damage. Regarding treatment, drugs currently available for the treatment of obesity are often inefficient and have adverse effects, so the search for new drugs for the treatment of metabolic diseases has been growing so much in recent years. In this context, organic compounds of selenium have been studied in the last decades, mainly due to their diverse pharmacological activities, among them, antioxidant, neuroprotective, anticancer, antiviral, immunosuppressive, antimicrobial, anxiolytic, antidepressant-like and anti-inflammatory. However, these compounds have recently attracted attention because of their beneficial effects on the regulation of metabolic homeostasis. The present thesis aimed to investigate the pharmacological effects of 4,4'-dichloro-diphenyl diselenide, (p-ClPhSe)2 in hyperglycemia and obesity models induced by the administration of fructose or monosodium glutamate (MSG) in rats. In the manuscript 1, an insulin-mimetic effect of (p-ClPhSe)2 was demonstrated in vitro; this compound stimulated the glucose uptake into skeletal muscle and its acute antihyperglycemic effect in a model of hyperglycemia induced by the administration of fructose in rats. Furthermore, in the manuscript 1, acute treatment with (p-ClPhSe)2 protected against liver metabolic alterations induced by fructose; this compound redirected the carbohydrate metabolism. In that sense, in the article 1, a homeostatic effect of subchronic treatment with (p-ClPhSe)2 was demonstrated, this compound reduced the first signs of obesity induced with the administration of GMS in rats. Whereas in the manuscript 2, it was possible to observe a hepatoprotective effect of subchronic treatment with (p-ClPhSe)2 against the mitochondrial dysfunction, oxidative stress and inflammation induced by the administration of GMS in rats. In addition, a beneficial effect of subchronic treatment with (p-ClPhSe)2 against metabolic dysfunction in blood, liver and skeletal muscle induced by the administration of GMS in rats was demonstrated in manuscript 3. Taken together, the present results demonstrated that the compound, (p-ClPhSe)2, has several pharmacological properties, such as antihyperglycemic, insulin-mimetic, anti-inflammatory and antioxidant. It is known that drugs used for the treatment of obesity are often inefficient due to the complications present during the progression of obesity. Considering the pharmacological effects of (p-ClPhSe)2 demonstrated in the present study, this organic compound of selenium may be a future therapeutic alternative for the treatment of this pathology and its complications.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA epidemia de obesidade é um problema de saúde pública mundial e é considerada uma das principais causas de morte e incapacidades em todo o mundo. Isso porque a patofisiologia dessa doença é extremamente complexa e envolve uma série de eventos que podem inclusive evoluir para um dano irreversível. Em relação ao tratamento, as drogas disponíveis, atualmente, para o tratamento da obesidade são muitas vezes ineficientes e apresentam efeitos adversos, por isso a busca por novos fármacos para o tratamento de doenças metabólicas vem crescendo nos últimos anos. Nesse contexto, os compostos orgânicos de selênio têm sido bastante estudados nas últimas décadas principalmente devido as suas diversas atividades farmacológicas, dentre elas, destaca-se as propriedades antioxidantes, neuroprotetora, anticâncer, antiviral, imunossupressora, antimicrobiana, ansiolítica, antidepressiva e anti-inflamatória. Entretanto, recentemente esses compostos têm chamado atenção devido aos seus efeitos benéficos na regulação da homeostase metabólica. Esta tese teve como objetivo investigar os efeitos farmacológicos do 4,4’-dicloro-difenil disseleneto, (p-ClPhSe)2 em modelos de hiperglicemia e obesidade induzidos pela administração de frutose ou glutamato monossódico (GMS) em ratos. No manuscrito 1 foi demonstrado um efeito insulino-mimético do (p-ClPhSe)2 in vitro, este composto estimulou a captação de glicose no músculo esquelético, bem como apresentou efeito anti-hiperglicêmico agudo em um modelo de hiperglicemia induzida pela administração de frutose em ratos. Além disso, no manuscrito 1, também foi demonstrado que o tratamento agudo com o (p-ClPhSe)2 protegeu das alterações metabólicas hepáticas induzidas pela frutose, através de um redirecionamento no metabolismo de carboidratos. Nesse sentido, no artigo 1 foi observado um efeito homeostático do tratamento subcrônico com o (p-ClPhSe)2 reduzindo os primeiros sinais de obesidade induzidos pela administração de GMS em ratos. Enquanto que, no manuscrito 2 foi possível observar um efeito hepatoprotetor do tratamento subcrônico com o (p-ClPhSe)2 na disfunção mitocondrial, no estresse oxidativo e na inflamação induzidos pela administração de GMS em ratos. Além disso, no manuscrito 3 foi demonstrado um efeito benéfico do tratamento subcrônico com o (p-ClPhSe.2 contra a disfunção metabólica no sangue, fígado e músculo esquelético induzida pela administração de GMS em ratos. Em conjunto, os resultados desta tese demonstram que o composto, (p-ClPhSe2 possui diversas propriedades farmacológicas, tais como, anti-hiperglicêmica, insulino-mimética, anti-inflamatória e antioxidante. Sabe-se que as drogas utilizadas para o tratamento da obesidade são muitas vezes ineficientes devido às complicações presentes durante a progressão da obesidade. Considerando os efeitos farmacológicos do (p-ClPhSe)2 demonstrados no presente estudo, esse composto orgânico de selênio pode ser uma futura alternativa terapêutica para o tratamento desta patologia e de suas complicações.Universidade Federal de Santa MariaBrasilBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaCentro de Ciências Naturais e ExatasNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Bem, Andreza Fabro dehttp://lattes.cnpq.br/0383092486694460Premaor, Melissa Orlandinhttp://lattes.cnpq.br/1919693261808995Mathias, Paulo Cezar de Freitashttp://lattes.cnpq.br/5279465385771687Emanuelli, Tatianahttp://lattes.cnpq.br/2165391096880394Quines, Caroline Brandão2019-09-25T20:06:53Z2019-09-25T20:06:53Z2017-03-03info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/18425porAttribution-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:UFSM2019-09-25T20:45:13Zoai:repositorio.ufsm.br:1/18425Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2019-09-25T20:45:13Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos Pharmacological action of 4,4'-dichloro-diphenyl diselenide in rat hyperglycemia and obesity models |
title |
Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos |
spellingShingle |
Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos Quines, Caroline Brandão Selênio Obesidade Alterações metabólicas Inflamação Estresse oxidativo Selenium Obesity Metabolic alterations Inflammation Oxidative stress Insulin-mimetic CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos |
title_full |
Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos |
title_fullStr |
Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos |
title_full_unstemmed |
Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos |
title_sort |
Ação farmacológica do 4,4’-dicloro-difenil disseleneto em modelos de hiperglicemia e obesidade em ratos |
author |
Quines, Caroline Brandão |
author_facet |
Quines, Caroline Brandão |
author_role |
author |
dc.contributor.none.fl_str_mv |
Nogueira, Cristina Wayne http://lattes.cnpq.br/2877042401245169 Bem, Andreza Fabro de http://lattes.cnpq.br/0383092486694460 Premaor, Melissa Orlandin http://lattes.cnpq.br/1919693261808995 Mathias, Paulo Cezar de Freitas http://lattes.cnpq.br/5279465385771687 Emanuelli, Tatiana http://lattes.cnpq.br/2165391096880394 |
dc.contributor.author.fl_str_mv |
Quines, Caroline Brandão |
dc.subject.por.fl_str_mv |
Selênio Obesidade Alterações metabólicas Inflamação Estresse oxidativo Selenium Obesity Metabolic alterations Inflammation Oxidative stress Insulin-mimetic CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
Selênio Obesidade Alterações metabólicas Inflamação Estresse oxidativo Selenium Obesity Metabolic alterations Inflammation Oxidative stress Insulin-mimetic CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
The obesity epidemic is a worldwide public health problem and is considered one of the leading causes of death and disability worldwide. This is because the pathophysiology of this disease is extremely complex and involves a series of events in cascades that can even evolve into irreversible damage. Regarding treatment, drugs currently available for the treatment of obesity are often inefficient and have adverse effects, so the search for new drugs for the treatment of metabolic diseases has been growing so much in recent years. In this context, organic compounds of selenium have been studied in the last decades, mainly due to their diverse pharmacological activities, among them, antioxidant, neuroprotective, anticancer, antiviral, immunosuppressive, antimicrobial, anxiolytic, antidepressant-like and anti-inflammatory. However, these compounds have recently attracted attention because of their beneficial effects on the regulation of metabolic homeostasis. The present thesis aimed to investigate the pharmacological effects of 4,4'-dichloro-diphenyl diselenide, (p-ClPhSe)2 in hyperglycemia and obesity models induced by the administration of fructose or monosodium glutamate (MSG) in rats. In the manuscript 1, an insulin-mimetic effect of (p-ClPhSe)2 was demonstrated in vitro; this compound stimulated the glucose uptake into skeletal muscle and its acute antihyperglycemic effect in a model of hyperglycemia induced by the administration of fructose in rats. Furthermore, in the manuscript 1, acute treatment with (p-ClPhSe)2 protected against liver metabolic alterations induced by fructose; this compound redirected the carbohydrate metabolism. In that sense, in the article 1, a homeostatic effect of subchronic treatment with (p-ClPhSe)2 was demonstrated, this compound reduced the first signs of obesity induced with the administration of GMS in rats. Whereas in the manuscript 2, it was possible to observe a hepatoprotective effect of subchronic treatment with (p-ClPhSe)2 against the mitochondrial dysfunction, oxidative stress and inflammation induced by the administration of GMS in rats. In addition, a beneficial effect of subchronic treatment with (p-ClPhSe)2 against metabolic dysfunction in blood, liver and skeletal muscle induced by the administration of GMS in rats was demonstrated in manuscript 3. Taken together, the present results demonstrated that the compound, (p-ClPhSe)2, has several pharmacological properties, such as antihyperglycemic, insulin-mimetic, anti-inflammatory and antioxidant. It is known that drugs used for the treatment of obesity are often inefficient due to the complications present during the progression of obesity. Considering the pharmacological effects of (p-ClPhSe)2 demonstrated in the present study, this organic compound of selenium may be a future therapeutic alternative for the treatment of this pathology and its complications. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-03-03 2019-09-25T20:06:53Z 2019-09-25T20:06:53Z |
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/1/18425 |
url |
http://repositorio.ufsm.br/handle/1/18425 |
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 Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica Centro de Ciências Naturais e Exatas |
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 |
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UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
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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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1805922169792757760 |