Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato

Detalhes bibliográficos
Autor(a) principal: Guimaraes Filho, Artur
Data de Publicação: 2012
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
dARK ID: ark:/83112/001300001ts97
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/7681
Resumo: Studies have shown that partial hepatectomia (HP) with removal of two thirds of the organ, in rodents, is followed by growth of remnant liver. In eukaryotic cells the enzyme malate dehydrogenase, from Krebs cycle, can be found in the cytoplasm (cytoplasmic malate dehydrogenase (MDH1) and in the mitochondrial matrix mitochondrial malate dehydrogenase (MDH2). Ammonia, a chemical compound that is toxic to animals, is produced in the course of metabolism. The liver actively participates in the mechanism of detoxification of ammonia. Two enzymes are involved in the disposal of excess ammonia in the cytosol: the glutamate dehydrogenase and glutamine synthetase which reduce α-ketoglutarate (AKG) to glutamate and glutamate to glutamine (GLN), respectively. Considering the effects of AKG and GLN in the liver of rodents, this study aims at assessing the metabolic enzyme changes that take place in regenerating livers after HP in rats treated with these amino acids. Anesthetized rats (Ketamine 50mg/mL + Xilazine 2% -1:0,5 mL) were submitted to HP and treated with calcium caseinate (CCA), L-glutamine (GLN) or ornithine alpha ketoglutarate (OKG) solutions administered by gavage, according to weight of each animal (0, 5gKg). One hundred and eight rats were distributed in 6 groups (n=18) and named according to the treatment used: G-1= Laparotomy (LAP) + CCA; G-2-HP+CCA; G-3 = LAP + GLN; G-4 HP + GLN; G-5 = LAP +ACG; G-6 = HP + ACG. Each group was redistributed into 3 subgroups. Blood and liver samples were collected on the 3rd, 7th and 14th postoperative days for quantification of metabolites (glucose, ketone bodies, lactate, pyruvate and ATP) and enzymes (MDH1 and MDH2). There was an increase of glycemia in 3rd day both in rats subjected to LAP and treated with ACG (G-5) as well as those submitted to HP and treated with GLN (G-3). There was significant reduction in expression of MDH1 enzyme in the liver in the 3rd and 14th day in rats subjected to LAP and treated with ACG and GLN (G-5 and G-3) compared to the control G-1 as well as in the expression of the enzyme MDH2 in 3rd day in the liver of G-6 and G-2 rats. Moreover no changes occurred in the expression of MDH2 in Group G-4 in relation to G-2. It is concluded that the surgical trauma in animals subjected to LAP or HP and treated with ACG or GLN induces increased glycemia in post-operative stage. ACG or GLN promotes reduction in expression of MDH1 enzyme in the liver of rats subjected to surgical trauma in 3rd and 14 days post surgery. ACG promotes reduction in the expression of MDH2 in the liver of rats undergoing HP or LAP only on the 3rd and 14 days post surgery, respectively. GLN given to HP rats does not alter the expression of MDH2 in the liver during the first 14 days post surgery.
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spelling Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-CetoglutaratoEnzymatic and metabolic changes in liver regeneration in rats fed with a diet supplement of l-glutamine and alpha ketoglutarateHepatectomiaGlutaminaRegeneração HepáticaStudies have shown that partial hepatectomia (HP) with removal of two thirds of the organ, in rodents, is followed by growth of remnant liver. In eukaryotic cells the enzyme malate dehydrogenase, from Krebs cycle, can be found in the cytoplasm (cytoplasmic malate dehydrogenase (MDH1) and in the mitochondrial matrix mitochondrial malate dehydrogenase (MDH2). Ammonia, a chemical compound that is toxic to animals, is produced in the course of metabolism. The liver actively participates in the mechanism of detoxification of ammonia. Two enzymes are involved in the disposal of excess ammonia in the cytosol: the glutamate dehydrogenase and glutamine synthetase which reduce α-ketoglutarate (AKG) to glutamate and glutamate to glutamine (GLN), respectively. Considering the effects of AKG and GLN in the liver of rodents, this study aims at assessing the metabolic enzyme changes that take place in regenerating livers after HP in rats treated with these amino acids. Anesthetized rats (Ketamine 50mg/mL + Xilazine 2% -1:0,5 mL) were submitted to HP and treated with calcium caseinate (CCA), L-glutamine (GLN) or ornithine alpha ketoglutarate (OKG) solutions administered by gavage, according to weight of each animal (0, 5gKg). One hundred and eight rats were distributed in 6 groups (n=18) and named according to the treatment used: G-1= Laparotomy (LAP) + CCA; G-2-HP+CCA; G-3 = LAP + GLN; G-4 HP + GLN; G-5 = LAP +ACG; G-6 = HP + ACG. Each group was redistributed into 3 subgroups. Blood and liver samples were collected on the 3rd, 7th and 14th postoperative days for quantification of metabolites (glucose, ketone bodies, lactate, pyruvate and ATP) and enzymes (MDH1 and MDH2). There was an increase of glycemia in 3rd day both in rats subjected to LAP and treated with ACG (G-5) as well as those submitted to HP and treated with GLN (G-3). There was significant reduction in expression of MDH1 enzyme in the liver in the 3rd and 14th day in rats subjected to LAP and treated with ACG and GLN (G-5 and G-3) compared to the control G-1 as well as in the expression of the enzyme MDH2 in 3rd day in the liver of G-6 and G-2 rats. Moreover no changes occurred in the expression of MDH2 in Group G-4 in relation to G-2. It is concluded that the surgical trauma in animals subjected to LAP or HP and treated with ACG or GLN induces increased glycemia in post-operative stage. ACG or GLN promotes reduction in expression of MDH1 enzyme in the liver of rats subjected to surgical trauma in 3rd and 14 days post surgery. ACG promotes reduction in the expression of MDH2 in the liver of rats undergoing HP or LAP only on the 3rd and 14 days post surgery, respectively. GLN given to HP rats does not alter the expression of MDH2 in the liver during the first 14 days post surgery.Estudos demonstraram que a hepatectomia parcial (HP) com remoção de dois terços do órgão, em roedores, é seguida por crescimento do fígado remanescente. Em células eucariontes a enzima malato desidrogenase, do ciclo de Krebs, pode ser encontrada no citoplasma (malato desidrogenase citoplásmica – (MDH1) e na matriz mitocondrial (malato desidrogenase mitocondrial - MDH2). A amônia, um composto químico tóxico para os animais, é produzida no curso do metabolismo. O fígado participa ativamente do mecanismo de detoxificação da amônia. Duas enzimas participam da eliminação do excesso de amônia do citosol: a glutamato desidrogenase e a glutamina sintetase que reduzem o alfa-cetoglutarato (ACG) em glutamato e glutamato em glutamina (GLN), respectivamente. Considerando os efeitos do ACG e da GLN no fígado de roedores, este estudo tem como objetivo avaliar as alterações metabólicas e enzimáticas observadas em fígados em regeneração após HP em ratos tratados com esses aminoácidos. Ratos anestesiados (Ketamina 50mg/mL + Xilazina 2% -1:0,5 mL) foram submetidos a HP e tratados com soluções de caseinato de cálcio (CCA), L-glutamina (GLN) ou ornitina alfa cetoglutarato (OKG), administradas por gavagem, de acordo com massa de cada animal (0,5g/Kg). Cento e oito ratos foram distribuídos em 6 grupos (n=18) e denominados conforme o tratamento usado: G-1= Laparotomia (LAP) + CCA; G-2= HP + CCA; G-3 = LAP + GLN; G-4 = HP + GLN; G-5= LAP + ACG; G-6 = HP + ACG. Cada grupo foi redistribuído em 3 subgrupos. Amostras (sangue e fígado) foram coletadas no 3º, 7º e 14º dias do pós-operatório, para quantificação de metabólitos (glicose, corpos cetônicos, piruvato, lactato e ATP) e enzimas (MDH1 e MDH2). Houve aumento da glicemia no 3º dia tanto nos ratos submetidos a LAP e tratados com ACG (G-5) bem como naqueles submetidos a HP e tratados com GLN (grupo G-3 ).Houve redução significante na expressão da enzima MDH1 no fígado no 3º e 14º dia nos ratos submetidos a LAP e tratados com ACG e GLN (G-5 e G-3) em relação ao controle G-1 bem como na expressão da enzima MDH2 no 3º dia no fígado dos ratos do G-6 em relação ao G-2. Também não foram observadas alterações na expressão da enzima MDH2 no grupo G-4 em relação ao grupo G-2. Conclui-se que o trauma cirúrgico em animais submetidos a LAP ou HP e tratados com ACG ou GLN induz aumento da glicemia na fase pós-operatoria. A oferta de ACG ou GLN promove redução na expressão da enzima MDH1 no fígado de ratos submetidos ao trauma cirúrgico no 3º e 14º dias pós cirurgia. A oferta de ACG promove redução na expressão da enzima MDH2 no fígado de ratos submetidos à HP ou somente LAP no 3º e 14º dias pós cirurgia, respectivamente. A oferta de GLN à ratos hepatectomizados não altera a expressão da enzima MDH2 no fígado desses animais nos primeiros 14 dias pós cirurgia.Guimarães, Sérgio BotelhoCunha, Rodrigo Maranguape Silva daGuimaraes Filho, Artur2014-03-14T16:49:17Z2014-03-14T16:49:17Z2012info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfGUIMARÃES FILHO, Artur. Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato. 2012. 181 f. Tese (Doutorado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2012.http://www.repositorio.ufc.br/handle/riufc/7681ark:/83112/001300001ts97porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2018-12-14T17:11:54Zoai:repositorio.ufc.br:riufc/7681Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T18:53:39.592683Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato
Enzymatic and metabolic changes in liver regeneration in rats fed with a diet supplement of l-glutamine and alpha ketoglutarate
title Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato
spellingShingle Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato
Guimaraes Filho, Artur
Hepatectomia
Glutamina
Regeneração Hepática
title_short Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato
title_full Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato
title_fullStr Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato
title_full_unstemmed Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato
title_sort Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato
author Guimaraes Filho, Artur
author_facet Guimaraes Filho, Artur
author_role author
dc.contributor.none.fl_str_mv Guimarães, Sérgio Botelho
Cunha, Rodrigo Maranguape Silva da
dc.contributor.author.fl_str_mv Guimaraes Filho, Artur
dc.subject.por.fl_str_mv Hepatectomia
Glutamina
Regeneração Hepática
topic Hepatectomia
Glutamina
Regeneração Hepática
description Studies have shown that partial hepatectomia (HP) with removal of two thirds of the organ, in rodents, is followed by growth of remnant liver. In eukaryotic cells the enzyme malate dehydrogenase, from Krebs cycle, can be found in the cytoplasm (cytoplasmic malate dehydrogenase (MDH1) and in the mitochondrial matrix mitochondrial malate dehydrogenase (MDH2). Ammonia, a chemical compound that is toxic to animals, is produced in the course of metabolism. The liver actively participates in the mechanism of detoxification of ammonia. Two enzymes are involved in the disposal of excess ammonia in the cytosol: the glutamate dehydrogenase and glutamine synthetase which reduce α-ketoglutarate (AKG) to glutamate and glutamate to glutamine (GLN), respectively. Considering the effects of AKG and GLN in the liver of rodents, this study aims at assessing the metabolic enzyme changes that take place in regenerating livers after HP in rats treated with these amino acids. Anesthetized rats (Ketamine 50mg/mL + Xilazine 2% -1:0,5 mL) were submitted to HP and treated with calcium caseinate (CCA), L-glutamine (GLN) or ornithine alpha ketoglutarate (OKG) solutions administered by gavage, according to weight of each animal (0, 5gKg). One hundred and eight rats were distributed in 6 groups (n=18) and named according to the treatment used: G-1= Laparotomy (LAP) + CCA; G-2-HP+CCA; G-3 = LAP + GLN; G-4 HP + GLN; G-5 = LAP +ACG; G-6 = HP + ACG. Each group was redistributed into 3 subgroups. Blood and liver samples were collected on the 3rd, 7th and 14th postoperative days for quantification of metabolites (glucose, ketone bodies, lactate, pyruvate and ATP) and enzymes (MDH1 and MDH2). There was an increase of glycemia in 3rd day both in rats subjected to LAP and treated with ACG (G-5) as well as those submitted to HP and treated with GLN (G-3). There was significant reduction in expression of MDH1 enzyme in the liver in the 3rd and 14th day in rats subjected to LAP and treated with ACG and GLN (G-5 and G-3) compared to the control G-1 as well as in the expression of the enzyme MDH2 in 3rd day in the liver of G-6 and G-2 rats. Moreover no changes occurred in the expression of MDH2 in Group G-4 in relation to G-2. It is concluded that the surgical trauma in animals subjected to LAP or HP and treated with ACG or GLN induces increased glycemia in post-operative stage. ACG or GLN promotes reduction in expression of MDH1 enzyme in the liver of rats subjected to surgical trauma in 3rd and 14 days post surgery. ACG promotes reduction in the expression of MDH2 in the liver of rats undergoing HP or LAP only on the 3rd and 14 days post surgery, respectively. GLN given to HP rats does not alter the expression of MDH2 in the liver during the first 14 days post surgery.
publishDate 2012
dc.date.none.fl_str_mv 2012
2014-03-14T16:49:17Z
2014-03-14T16:49:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
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dc.identifier.uri.fl_str_mv GUIMARÃES FILHO, Artur. Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato. 2012. 181 f. Tese (Doutorado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2012.
http://www.repositorio.ufc.br/handle/riufc/7681
dc.identifier.dark.fl_str_mv ark:/83112/001300001ts97
identifier_str_mv GUIMARÃES FILHO, Artur. Alterações metabólicas e enzimáticas na regeneração hepática em ratos alimentados com dietas suplementar de L-Glutamina e Alfa-Cetoglutarato. 2012. 181 f. Tese (Doutorado em Cirurgia) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2012.
ark:/83112/001300001ts97
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