Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações do UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/11193 |
Resumo: | The diazinon (DI) is a commonly organophosphorus (OP) used in pest control around the world. Severe acute poisoning due to ingestion of OP in suicide attempts were reported during the past years. The main toxic effect of OP is through acetylcholinesterase (AChE) inhibition, leading to a greater stimulation of cholinergic synapses in the central nervous system (CNS) which can lead to death. However, poisoning can lead to such state of hyperglycemia. However, the mechanism by which OP lead to this adverse effect is still unknown, even so, it is suggested that glycogenolysis and neoglycogenic pathways are involved. In recent studies, ebselen (EB) has shown pharmacological properties in experimental models of genetically or alloxan induced diabetes, as well as complications resulting from diabetes. Being considered a potential pharmacological agent for hyperglycemia treatment when caused by OP poisoning. Thus, this study evaluated the effects of EB on the glucose metabolism and other biochemical changes induced in rats by DI, as well as the insulin-mimetic effect of EB on glucose uptake in skeletal muscle tissue and the synthesis and breakdown of liver glycogen in tissues of rats. In in vivo experiments, rats were pretreated with a single injection of EB (50 mg/kg) intraperitoneally (i.p.). Thereafter, the animals were treated with a single oral (p.o.) dose of DI (200 mg/kg). Parameters indicative of liver and pancreas damage such as amylase, lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities and serum glucose, hepatic glycogen content and hepatic glucose-6-phosphatase (G6Pase) activity were determined. Pretreatment with EB was effective in preventing against pancreatic and liver damage, as shown by the reduction in the activities of amylase, lipase, AST, ALT, ALP and LDH. EB was able to reduce blood glucose and hepatic glycogen content increased in the animals exposed to DI. In in vitro assays, EB (150 mM) or insulin (IN 10 mM as a positive control) were incubated with either skeletal muscle or liver tissue, in order to measure the absorption of glucose, glycogen synthesis and glycogen breakdown. Thus, EB increased glucose uptake in skeletal muscle, stimulated glycogen synthesis and inhibited hepatic glycogen breakdown in a manner similar to IN. In this context, EB demonstrated insulin-mimetic properties, lowering blood glucose levels in vivo and increasing glucose uptake by skeletal tissue, increasing glycogen synthesis and decreasing glycogen degradation in vitro. In conclusion, EB, possibly through its insulin-mimetic action, protected against pancreatic and hepatic damage caused by DI in rats. |
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2012-12-142012-12-142012-03-01COSTA, Michael Daniel da. Ebselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic properties. 2012. 59 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/11193The diazinon (DI) is a commonly organophosphorus (OP) used in pest control around the world. Severe acute poisoning due to ingestion of OP in suicide attempts were reported during the past years. The main toxic effect of OP is through acetylcholinesterase (AChE) inhibition, leading to a greater stimulation of cholinergic synapses in the central nervous system (CNS) which can lead to death. However, poisoning can lead to such state of hyperglycemia. However, the mechanism by which OP lead to this adverse effect is still unknown, even so, it is suggested that glycogenolysis and neoglycogenic pathways are involved. In recent studies, ebselen (EB) has shown pharmacological properties in experimental models of genetically or alloxan induced diabetes, as well as complications resulting from diabetes. Being considered a potential pharmacological agent for hyperglycemia treatment when caused by OP poisoning. Thus, this study evaluated the effects of EB on the glucose metabolism and other biochemical changes induced in rats by DI, as well as the insulin-mimetic effect of EB on glucose uptake in skeletal muscle tissue and the synthesis and breakdown of liver glycogen in tissues of rats. In in vivo experiments, rats were pretreated with a single injection of EB (50 mg/kg) intraperitoneally (i.p.). Thereafter, the animals were treated with a single oral (p.o.) dose of DI (200 mg/kg). Parameters indicative of liver and pancreas damage such as amylase, lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities and serum glucose, hepatic glycogen content and hepatic glucose-6-phosphatase (G6Pase) activity were determined. Pretreatment with EB was effective in preventing against pancreatic and liver damage, as shown by the reduction in the activities of amylase, lipase, AST, ALT, ALP and LDH. EB was able to reduce blood glucose and hepatic glycogen content increased in the animals exposed to DI. In in vitro assays, EB (150 mM) or insulin (IN 10 mM as a positive control) were incubated with either skeletal muscle or liver tissue, in order to measure the absorption of glucose, glycogen synthesis and glycogen breakdown. Thus, EB increased glucose uptake in skeletal muscle, stimulated glycogen synthesis and inhibited hepatic glycogen breakdown in a manner similar to IN. In this context, EB demonstrated insulin-mimetic properties, lowering blood glucose levels in vivo and increasing glucose uptake by skeletal tissue, increasing glycogen synthesis and decreasing glycogen degradation in vitro. In conclusion, EB, possibly through its insulin-mimetic action, protected against pancreatic and hepatic damage caused by DI in rats.O diazinon (DI) é um dos organofosforados (OP) mais utilizados no controle de pragas ao redor do mundo. Desta forma, são cotidianos os relatos de intoxicações acidentais por estes. Além disso, muitos casos de intoxicações devido à ingestão aguda por OP em tentativas de suicídio foram relatadas durante os últimos anos. Sabe-se que o principal efeito tóxico dos OP é através da inibição da acetilcolinesterase (AChE), levando a um maior estímulo das sinapses colinérgicas no sistema nervoso central (SNC) o que pode provocar à morte. A intoxicação por estes compostos também pode levar a um estado de hiperglicemia. Ainda desconhece-se o mecanismo pelo qual os OP levam a este efeito adverso, contudo, sugere-se que as vias da gliconeogênese e da glicogenólise estejam envolvidas. O ebselen (EB) apresentou propriedades benéficas em modelos experimentais de diabetes induzida com aloxano ou geneticamente, assim como contra complicações consequentes da diabetes. Sendo considerado assim, como um agente farmacológico em potencial para o tratamento da hiperglicemia provocada pela intoxicação por OP. Dessa forma, o presente trabalho avaliou os efeitos do EB in vivo no metabolismo da glicose e em outras alterações bioquímicas induzidas pelo DI em ratos, assim como, o efeito insulino-mimético do EB na captação de glicose em tecido muscular esquelético e na síntese e degradação do glicogênio hepático in vitro. Para os experimentos ex vivo, ratos Wistar machos adultos foram pré-tratados com uma única injeção de EB (50 mg/kg) pela via intraperitoneal (i.p.). Trinta minutos depois, os animais foram tratados com uma única dose de DI (200 mg/kg) pela via oral (v.o). Vinte e quatro horas após, parâmetros indicativos de dano pâncreatico e hepático, como as atividades da amilase, lipase, aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e lactato desidrogenase (LDH), bem como níveis séricos de glicose, conteúdo de glicogênio hepático e atividade da glicose-6-fosfatase (G6Pase) hepática foram determinados. O pré-tratamento com EB preveniu contra os danos pâncreaticos e hepáticos provocados pelo DI, como mostrado pela redução nas atividades da amilase, lipase, AST, ALT, ALP e LDH. Alem disso, o EB reduziu a hiperglicemia, a qual foi aumentada nos animais expostos ao DI e aumentou o conteúdo de glicogênio hepático, o qual tinha diminuido nestes. Em ensaios in vitro, o EB (150 mM) ou insulina (IN 10 mM, controle positivo) foram incubados com amostras de músculo esquelético ou tecido hepático, com o objetivo de medir a captação de glicose, síntese e quebra de glicogênio. Assim, o EB aumentou a captação de glicose pelo músculo esquelético, estimulou a síntese de glicogênio hepático e inibiu a quebra do glicogênio em uma maneira similar à IN. Neste contexto, o EB apresentou propriedades insulino-miméticas, diminuindo os níveis de glicose sérica in vivo e aumentando a captação de glicose pelo tecido esquelético, aumentando a síntese e diminuindo a quebra de glicogênio in vitro. Desta forma, o EB protegeu da hiperglicemia induzida por OP, agindo de uma forma mimética à insulina.Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaBioquímica toxicológicaOrganocalcogêniosPesticidas organofosforadosEbselenCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAEbselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratosEbselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic propertiesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Wagner, Carolinehttp://lattes.cnpq.br/4004565241849091Pereira, Maria Esterhttp://lattes.cnpq.br/9299114496157799http://lattes.cnpq.br/5163477755822028Costa, Michael Daniel da2008000000024005005005005000186436d-f662-4a5e-b36e-8c8ab8e10bf8f0caa433-cda3-44be-9349-97f2c2423fa2580e04d6-2496-45ed-86a2-aa0657b90282276bcfc2-822c-4d05-88f0-be6c067a20c1info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALCOSTA, MICHAEL DANIEL DA.pdfapplication/pdf412212http://repositorio.ufsm.br/bitstream/1/11193/1/COSTA%2c%20MICHAEL%20DANIEL%20DA.pdf49c7501a5665aafb36bd5fe5daa241ccMD51TEXTCOSTA, MICHAEL DANIEL DA.pdf.txtCOSTA, MICHAEL DANIEL DA.pdf.txtExtracted texttext/plain79663http://repositorio.ufsm.br/bitstream/1/11193/2/COSTA%2c%20MICHAEL%20DANIEL%20DA.pdf.txt244e3de186f7038098702f9d0573937cMD52THUMBNAILCOSTA, MICHAEL DANIEL DA.pdf.jpgCOSTA, MICHAEL DANIEL DA.pdf.jpgIM Thumbnailimage/jpeg5692http://repositorio.ufsm.br/bitstream/1/11193/3/COSTA%2c%20MICHAEL%20DANIEL%20DA.pdf.jpg38cb3ddcac4abd0725c80fa8bdaeac88MD531/111932023-06-23 14:43:52.812oai:repositorio.ufsm.br:1/11193Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2023-06-23T17:43:52Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos |
dc.title.alternative.eng.fl_str_mv |
Ebselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic properties |
title |
Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos |
spellingShingle |
Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos Costa, Michael Daniel da Bioquímica toxicológica Organocalcogênios Pesticidas organofosforados Ebselen CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos |
title_full |
Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos |
title_fullStr |
Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos |
title_full_unstemmed |
Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos |
title_sort |
Ebselen, um composto com propriedade insulino-mimética, reduz a hiperglicemia temporária induzida pelo diazinon em ratos |
author |
Costa, Michael Daniel da |
author_facet |
Costa, Michael Daniel da |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2877042401245169 |
dc.contributor.referee1.fl_str_mv |
Wagner, Caroline |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/4004565241849091 |
dc.contributor.referee2.fl_str_mv |
Pereira, Maria Ester |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/9299114496157799 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5163477755822028 |
dc.contributor.author.fl_str_mv |
Costa, Michael Daniel da |
contributor_str_mv |
Nogueira, Cristina Wayne Wagner, Caroline Pereira, Maria Ester |
dc.subject.por.fl_str_mv |
Bioquímica toxicológica Organocalcogênios Pesticidas organofosforados Ebselen |
topic |
Bioquímica toxicológica Organocalcogênios Pesticidas organofosforados Ebselen CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
The diazinon (DI) is a commonly organophosphorus (OP) used in pest control around the world. Severe acute poisoning due to ingestion of OP in suicide attempts were reported during the past years. The main toxic effect of OP is through acetylcholinesterase (AChE) inhibition, leading to a greater stimulation of cholinergic synapses in the central nervous system (CNS) which can lead to death. However, poisoning can lead to such state of hyperglycemia. However, the mechanism by which OP lead to this adverse effect is still unknown, even so, it is suggested that glycogenolysis and neoglycogenic pathways are involved. In recent studies, ebselen (EB) has shown pharmacological properties in experimental models of genetically or alloxan induced diabetes, as well as complications resulting from diabetes. Being considered a potential pharmacological agent for hyperglycemia treatment when caused by OP poisoning. Thus, this study evaluated the effects of EB on the glucose metabolism and other biochemical changes induced in rats by DI, as well as the insulin-mimetic effect of EB on glucose uptake in skeletal muscle tissue and the synthesis and breakdown of liver glycogen in tissues of rats. In in vivo experiments, rats were pretreated with a single injection of EB (50 mg/kg) intraperitoneally (i.p.). Thereafter, the animals were treated with a single oral (p.o.) dose of DI (200 mg/kg). Parameters indicative of liver and pancreas damage such as amylase, lipase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities and serum glucose, hepatic glycogen content and hepatic glucose-6-phosphatase (G6Pase) activity were determined. Pretreatment with EB was effective in preventing against pancreatic and liver damage, as shown by the reduction in the activities of amylase, lipase, AST, ALT, ALP and LDH. EB was able to reduce blood glucose and hepatic glycogen content increased in the animals exposed to DI. In in vitro assays, EB (150 mM) or insulin (IN 10 mM as a positive control) were incubated with either skeletal muscle or liver tissue, in order to measure the absorption of glucose, glycogen synthesis and glycogen breakdown. Thus, EB increased glucose uptake in skeletal muscle, stimulated glycogen synthesis and inhibited hepatic glycogen breakdown in a manner similar to IN. In this context, EB demonstrated insulin-mimetic properties, lowering blood glucose levels in vivo and increasing glucose uptake by skeletal tissue, increasing glycogen synthesis and decreasing glycogen degradation in vitro. In conclusion, EB, possibly through its insulin-mimetic action, protected against pancreatic and hepatic damage caused by DI in rats. |
publishDate |
2012 |
dc.date.accessioned.fl_str_mv |
2012-12-14 |
dc.date.available.fl_str_mv |
2012-12-14 |
dc.date.issued.fl_str_mv |
2012-03-01 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
COSTA, Michael Daniel da. Ebselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic properties. 2012. 59 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/11193 |
identifier_str_mv |
COSTA, Michael Daniel da. Ebselen reduces hyperglycemia temporarily-induced by diazinon: a compound with insulin-mimetic properties. 2012. 59 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
url |
http://repositorio.ufsm.br/handle/1/11193 |
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por |
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por |
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400 500 500 500 500 |
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Universidade Federal de Santa Maria |
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UFSM |
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Bioquímica |
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Universidade Federal de Santa Maria |
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