Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica

Detalhes bibliográficos
Autor(a) principal: Maria Juracy Solon Petrola
Data de Publicação: 2011
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFC
Texto Completo: http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10856
Resumo: Chronic myeloid leukemia (CML) is characterized by clonal expansion of hematopoietic progenitor cells, result from the translocation (9:22). The oncogene BCR-ABL, in the Ph chromosome, is transcribed and translated into a fusion protein BCR / ABL. The ABL tyrosine kinase (TK) in the fusion protein is constitutively activated and is needed for the initial leukemogenic event of CML and its activity induces production of reactive oxygen species (ROS). Of particular relevance to CML is the fact that an increase of ROS can have consequences, facilitating genomic instability may contribute to disease progression. The aim of this study was to determine the oxidative status in patients with CML, in attendance at a university hospital (HUWC). This is a cross-sectional study consisted of 30 adult patients of both sexes with clinical and laboratory diagnosis of CML on treatment with inhibitors (TK) 1st and 2nd generation. The concentrations of malondialdehyde (MDA) and nitrite (NO2-) were performed by spectrophotometric method. The activities of enzymes glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in hemolysate by Glutathione Peroxidase Cellular Activity Kit  Assay (Sigma-Aldrich) and spectrophotometry, respectively. Total glutathione, reduced glutathione (reduced GSH), glutathione (GSSG) were determined by Total Glutathione Activity Kit  (Assay Designs, Inc) and calculated the ratio GSH / GSSG. For statistical analysis of nonparametric data was used  and ANOVA test for multiple comparisons Tukey. It was considered the minimum level of significance of 5%. The average concentrations of NO2- and MDA were increased in CML patients compared to control, regardless of disease activity. The antioxidant profile was characterized by decreased CAT and GSH-Px increased also independent of disease activity. The reduced GSH is presented decreased, the GSSH, increased and GSH / GSSG decreased. It was observed that patients using protease inhibitors of TK 2nd generation of oxidative stress parameters were significantly elevated compared to controls. In the analysis of patients on imatinib were not detected significant changes in oxidative status. We conclude that patients with CML are under oxidative stress and impaired antioxidant activity.
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spelling info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisPerfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnicaProfile of oxidative stress in patients with chronic myeloid leukemia2011-05-31RomÃlia Pinheiro GonÃalves Lemes28620062387http://lattes.cnpq.br/8202510508068072Josà Ajax Nogueira Queiroz10221433368http://lattes.cnpq.br/6534805938502619Margarida Maria de Lima Pompeu11779420382Maria da Silva Pitombeira00117412368http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4787973H911314885391Maria Juracy Solon PetrolaUniversidade Federal do CearÃPrograma de PÃs-GraduaÃÃo em PatologiaUFCBRLeukemia Myelogenous Chronic BCR-ABL Positive Oxidative Stress Protein-Tyrosine KinasesHEMATOLOGIAChronic myeloid leukemia (CML) is characterized by clonal expansion of hematopoietic progenitor cells, result from the translocation (9:22). The oncogene BCR-ABL, in the Ph chromosome, is transcribed and translated into a fusion protein BCR / ABL. The ABL tyrosine kinase (TK) in the fusion protein is constitutively activated and is needed for the initial leukemogenic event of CML and its activity induces production of reactive oxygen species (ROS). Of particular relevance to CML is the fact that an increase of ROS can have consequences, facilitating genomic instability may contribute to disease progression. The aim of this study was to determine the oxidative status in patients with CML, in attendance at a university hospital (HUWC). This is a cross-sectional study consisted of 30 adult patients of both sexes with clinical and laboratory diagnosis of CML on treatment with inhibitors (TK) 1st and 2nd generation. The concentrations of malondialdehyde (MDA) and nitrite (NO2-) were performed by spectrophotometric method. The activities of enzymes glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in hemolysate by Glutathione Peroxidase Cellular Activity Kit  Assay (Sigma-Aldrich) and spectrophotometry, respectively. Total glutathione, reduced glutathione (reduced GSH), glutathione (GSSG) were determined by Total Glutathione Activity Kit  (Assay Designs, Inc) and calculated the ratio GSH / GSSG. For statistical analysis of nonparametric data was used  and ANOVA test for multiple comparisons Tukey. It was considered the minimum level of significance of 5%. The average concentrations of NO2- and MDA were increased in CML patients compared to control, regardless of disease activity. The antioxidant profile was characterized by decreased CAT and GSH-Px increased also independent of disease activity. The reduced GSH is presented decreased, the GSSH, increased and GSH / GSSG decreased. It was observed that patients using protease inhibitors of TK 2nd generation of oxidative stress parameters were significantly elevated compared to controls. In the analysis of patients on imatinib were not detected significant changes in oxidative status. We conclude that patients with CML are under oxidative stress and impaired antioxidant activity. A Leucemia mielÃide crÃnica (LMC) à caracterizada pela expansÃo clonal de cÃlulas progenitoras hematopoÃticas, resultante da translocaÃÃo (9:22). O oncogene de fusÃo BCR-ABL, no cromossomo Ph, à transcrito e traduzido numa proteÃna de fusÃo BCR/ABL. A tirosina quinase (TK) ABL na proteÃna de fusÃo à constitutivamente ativada sendo necessÃria para os eventos leucemogÃnicos iniciais da LMC e sua atividade induz a produÃÃo de espÃcies reativas de oxigÃnio (EROs). De particular relevÃncia para LMC à o fato de que um aumento de EROs pode ter consequÃncias, facilitando a instabilidade genÃmica podendo contribuir para a progressÃo da doenÃa. O objetivo do estudo foi determinar o perfil oxidativo em pacientes com LMC, em acompanhamento ambulatorial no Hospital UniversitÃrio Walter CantÃdio (HUWC). Trata-se de um estudo transversal constituÃdo de 30 pacientes adultos, com diagnostico clÃnico e laboratorial de LMC, em tratamento com inibidores de (TK) de 1 e 2 geraÃÃo. As concentraÃÃes de malonaldeÃdo (MDA) e de nitrito (NO2-) foram realizadas por mÃtodo espectofotomÃtrico. As atividades das enzimas Glutationa peroxidase (GSH-Px) e catalase (CAT) foram determinadas no hemolisado, por kit Glutathione Peroxidase Cellular Activity Assay (Sigma-Aldrich) e por espectofotometria, respectivamente. Glutationa total, glutationa reduzida (GSH reduzida), glutationa oxidada (GSSG) foram determinadas por kit Total Glutathione Activity (Assay Designs, Inc) e calculada a relaÃÃo GSH/GSSG. Para a anÃlise estatÃstica de dados nÃo paramÃtricos foi utilizado o ANOVA e o teste de mÃltiplas comparaÃÃes de Tukey. Foi considerado o nÃvel mÃnimo de significÃncia de 5%. As concentraÃÃes mÃdia de MDA e de NO2- foram aumentadas nos pacientes com LMC em relaÃÃo ao controle, independente da atividade da doenÃa. O perfil antioxidante foi caracterizado pela diminuiÃÃo da CAT e aumento da GSH-Px tambÃm independente da atividade da doenÃa. A GSH reduzida se apresentou diminuÃda, a GSSH, aumentada e a relaÃÃo GSH/GSSG diminuÃda. Os pacientes em uso de inibidores de TK de 2 geraÃÃo apresentaram parÃmetros do estresse oxidativo significativamente elevados em relaÃÃo ao grupo controle. Conclui-se que os pacientes com LMC estÃo sob estresse oxidativo e com atividade antioxidante comprometida. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=10856application/pdfinfo:eu-repo/semantics/openAccessporreponame:Biblioteca Digital de Teses e Dissertações da UFCinstname:Universidade Federal do Cearáinstacron:UFC2019-01-21T11:24:01Zmail@mail.com -
dc.title.pt.fl_str_mv Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica
dc.title.alternative..fl_str_mv Profile of oxidative stress in patients with chronic myeloid leukemia
title Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica
spellingShingle Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica
Maria Juracy Solon Petrola
Leukemia Myelogenous Chronic BCR-ABL Positive
Oxidative Stress
Protein-Tyrosine Kinases
HEMATOLOGIA
title_short Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica
title_full Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica
title_fullStr Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica
title_full_unstemmed Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica
title_sort Perfil do estresse oxidativo em pacientes portadores de Leucemia MielÃide CrÃnica
author Maria Juracy Solon Petrola
author_facet Maria Juracy Solon Petrola
author_role author
dc.contributor.advisor1.fl_str_mv RomÃlia Pinheiro GonÃalves Lemes
dc.contributor.advisor1ID.fl_str_mv 28620062387
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8202510508068072
dc.contributor.referee1.fl_str_mv Josà Ajax Nogueira Queiroz
dc.contributor.referee1ID.fl_str_mv 10221433368
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/6534805938502619
dc.contributor.referee2.fl_str_mv Margarida Maria de Lima Pompeu
dc.contributor.referee2ID.fl_str_mv 11779420382
dc.contributor.referee3.fl_str_mv Maria da Silva Pitombeira
dc.contributor.referee3ID.fl_str_mv 00117412368
dc.contributor.referee3Lattes.fl_str_mv http://buscatextual.cnpq.br/buscatextual/visualizacv.jsp?id=K4787973H9
dc.contributor.authorID.fl_str_mv 11314885391
dc.contributor.author.fl_str_mv Maria Juracy Solon Petrola
contributor_str_mv RomÃlia Pinheiro GonÃalves Lemes
Josà Ajax Nogueira Queiroz
Margarida Maria de Lima Pompeu
Maria da Silva Pitombeira
dc.subject.eng.fl_str_mv Leukemia Myelogenous Chronic BCR-ABL Positive
Oxidative Stress
Protein-Tyrosine Kinases
topic Leukemia Myelogenous Chronic BCR-ABL Positive
Oxidative Stress
Protein-Tyrosine Kinases
HEMATOLOGIA
dc.subject.cnpq.fl_str_mv HEMATOLOGIA
dc.description.abstract..fl_txt_mv Chronic myeloid leukemia (CML) is characterized by clonal expansion of hematopoietic progenitor cells, result from the translocation (9:22). The oncogene BCR-ABL, in the Ph chromosome, is transcribed and translated into a fusion protein BCR / ABL. The ABL tyrosine kinase (TK) in the fusion protein is constitutively activated and is needed for the initial leukemogenic event of CML and its activity induces production of reactive oxygen species (ROS). Of particular relevance to CML is the fact that an increase of ROS can have consequences, facilitating genomic instability may contribute to disease progression. The aim of this study was to determine the oxidative status in patients with CML, in attendance at a university hospital (HUWC). This is a cross-sectional study consisted of 30 adult patients of both sexes with clinical and laboratory diagnosis of CML on treatment with inhibitors (TK) 1st and 2nd generation. The concentrations of malondialdehyde (MDA) and nitrite (NO2-) were performed by spectrophotometric method. The activities of enzymes glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in hemolysate by Glutathione Peroxidase Cellular Activity Kit  Assay (Sigma-Aldrich) and spectrophotometry, respectively. Total glutathione, reduced glutathione (reduced GSH), glutathione (GSSG) were determined by Total Glutathione Activity Kit  (Assay Designs, Inc) and calculated the ratio GSH / GSSG. For statistical analysis of nonparametric data was used  and ANOVA test for multiple comparisons Tukey. It was considered the minimum level of significance of 5%. The average concentrations of NO2- and MDA were increased in CML patients compared to control, regardless of disease activity. The antioxidant profile was characterized by decreased CAT and GSH-Px increased also independent of disease activity. The reduced GSH is presented decreased, the GSSH, increased and GSH / GSSG decreased. It was observed that patients using protease inhibitors of TK 2nd generation of oxidative stress parameters were significantly elevated compared to controls. In the analysis of patients on imatinib were not detected significant changes in oxidative status. We conclude that patients with CML are under oxidative stress and impaired antioxidant activity.
dc.description.abstract.por.fl_txt_mv A Leucemia mielÃide crÃnica (LMC) à caracterizada pela expansÃo clonal de cÃlulas progenitoras hematopoÃticas, resultante da translocaÃÃo (9:22). O oncogene de fusÃo BCR-ABL, no cromossomo Ph, à transcrito e traduzido numa proteÃna de fusÃo BCR/ABL. A tirosina quinase (TK) ABL na proteÃna de fusÃo à constitutivamente ativada sendo necessÃria para os eventos leucemogÃnicos iniciais da LMC e sua atividade induz a produÃÃo de espÃcies reativas de oxigÃnio (EROs). De particular relevÃncia para LMC à o fato de que um aumento de EROs pode ter consequÃncias, facilitando a instabilidade genÃmica podendo contribuir para a progressÃo da doenÃa. O objetivo do estudo foi determinar o perfil oxidativo em pacientes com LMC, em acompanhamento ambulatorial no Hospital UniversitÃrio Walter CantÃdio (HUWC). Trata-se de um estudo transversal constituÃdo de 30 pacientes adultos, com diagnostico clÃnico e laboratorial de LMC, em tratamento com inibidores de (TK) de 1 e 2 geraÃÃo. As concentraÃÃes de malonaldeÃdo (MDA) e de nitrito (NO2-) foram realizadas por mÃtodo espectofotomÃtrico. As atividades das enzimas Glutationa peroxidase (GSH-Px) e catalase (CAT) foram determinadas no hemolisado, por kit Glutathione Peroxidase Cellular Activity Assay (Sigma-Aldrich) e por espectofotometria, respectivamente. Glutationa total, glutationa reduzida (GSH reduzida), glutationa oxidada (GSSG) foram determinadas por kit Total Glutathione Activity (Assay Designs, Inc) e calculada a relaÃÃo GSH/GSSG. Para a anÃlise estatÃstica de dados nÃo paramÃtricos foi utilizado o ANOVA e o teste de mÃltiplas comparaÃÃes de Tukey. Foi considerado o nÃvel mÃnimo de significÃncia de 5%. As concentraÃÃes mÃdia de MDA e de NO2- foram aumentadas nos pacientes com LMC em relaÃÃo ao controle, independente da atividade da doenÃa. O perfil antioxidante foi caracterizado pela diminuiÃÃo da CAT e aumento da GSH-Px tambÃm independente da atividade da doenÃa. A GSH reduzida se apresentou diminuÃda, a GSSH, aumentada e a relaÃÃo GSH/GSSG diminuÃda. Os pacientes em uso de inibidores de TK de 2 geraÃÃo apresentaram parÃmetros do estresse oxidativo significativamente elevados em relaÃÃo ao grupo controle. Conclui-se que os pacientes com LMC estÃo sob estresse oxidativo e com atividade antioxidante comprometida.
description Chronic myeloid leukemia (CML) is characterized by clonal expansion of hematopoietic progenitor cells, result from the translocation (9:22). The oncogene BCR-ABL, in the Ph chromosome, is transcribed and translated into a fusion protein BCR / ABL. The ABL tyrosine kinase (TK) in the fusion protein is constitutively activated and is needed for the initial leukemogenic event of CML and its activity induces production of reactive oxygen species (ROS). Of particular relevance to CML is the fact that an increase of ROS can have consequences, facilitating genomic instability may contribute to disease progression. The aim of this study was to determine the oxidative status in patients with CML, in attendance at a university hospital (HUWC). This is a cross-sectional study consisted of 30 adult patients of both sexes with clinical and laboratory diagnosis of CML on treatment with inhibitors (TK) 1st and 2nd generation. The concentrations of malondialdehyde (MDA) and nitrite (NO2-) were performed by spectrophotometric method. The activities of enzymes glutathione peroxidase (GSH-Px) and catalase (CAT) were determined in hemolysate by Glutathione Peroxidase Cellular Activity Kit  Assay (Sigma-Aldrich) and spectrophotometry, respectively. Total glutathione, reduced glutathione (reduced GSH), glutathione (GSSG) were determined by Total Glutathione Activity Kit  (Assay Designs, Inc) and calculated the ratio GSH / GSSG. For statistical analysis of nonparametric data was used  and ANOVA test for multiple comparisons Tukey. It was considered the minimum level of significance of 5%. The average concentrations of NO2- and MDA were increased in CML patients compared to control, regardless of disease activity. The antioxidant profile was characterized by decreased CAT and GSH-Px increased also independent of disease activity. The reduced GSH is presented decreased, the GSSH, increased and GSH / GSSG decreased. It was observed that patients using protease inhibitors of TK 2nd generation of oxidative stress parameters were significantly elevated compared to controls. In the analysis of patients on imatinib were not detected significant changes in oxidative status. We conclude that patients with CML are under oxidative stress and impaired antioxidant activity.
publishDate 2011
dc.date.issued.fl_str_mv 2011-05-31
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dc.publisher.program.fl_str_mv Programa de PÃs-GraduaÃÃo em Patologia
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publisher.none.fl_str_mv Universidade Federal do CearÃ
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