Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme

Detalhes bibliográficos
Ano de defesa: 2011
Autor(a) principal: Santos, Bruna Stefânia Carvalho dos
Orientador(a): Gonçalves, Romélia Pinheiro
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/7053
Resumo: The sickle cell anemia is one of the most common genetic disorders in our country. The -globin haplotypes are associated with the clinical heterogeneity of the disease. Individuals with sickle cell disease are subjected to high levels of oxidative stress. Hydroxyurea (HU) has been used as treatment and it increases the levels of fetal hemoglobin having an action antioxidant. The study aimed to investigate the impact of the use of HU and haplotypes in the oxidative status in patients with sickle cell anemia. Samples from 64 patients treated at the University Hospital Walter Cantídio - HUWC and the control group of 20 individuals without hemoglobinopathies. Patients were stratified into groups: the first one using HU > 1 year, the second using HU ≤ 1 year and the third using of HU (SHU). Confirmation of the diagnosis and analysis of haplotypes were performed by molecular study. The measurements of nitrite (NO2-), malonaldehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione total (GSSG+GSH), oxidized (GSSG) and reduced (GSH) and the ratio GSSG/GSH (glutathione oxidized/reduced) were performed by spectrophotometry. Mean levels of NO2- and MDA were shown to be higher in SHU group, being significant only for MDA (p < 0,05). The assessment of oxidative stress in relation to haplotypes showed that the population without the use of HU levels of NO2- and MDA were similar between groups, with an insignificant increase of GSH-Px in the Bantu/n compared with Benin/n and index GSSG/GSH in the Benin/n compared with Bantu/n. In the population using the HU there was a nonsignificant increase in the levels of NO2- in the Bantu/n compared with Benin/n with similar results between groups of MDA and a significant increase in GSH-Px (p <0.03) in the Benin/n compared with Bantu/n. The results of CAT were similar between groups. The ratio of GSSG/GSH was higher but not significant in the Bantu/n compared to Benin/n. The results of this study support the hypothesis that patients with the sickle cell anemia have a state hiperoxidativo products with high levels of oxidative stress and decreased antioxidant status and that of hydroxyurea had an impact on oxidative stress. However, regarding the impact of the haplotypes in oxidative stress, further studies with a larger sample should be recommended to confirm our results, considering that the group of patients not treated with HU was lower than the group of patients using HU, the which may have interfered in the statistical analysis of results.
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spelling Santos, Bruna Stefânia Carvalho dosGonçalves, Romélia Pinheiro2014-01-06T11:49:18Z2014-01-06T11:49:18Z2011SANTOS, B. S. C. Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme. 2011. 96 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2011.http://www.repositorio.ufc.br/handle/riufc/7053The sickle cell anemia is one of the most common genetic disorders in our country. The -globin haplotypes are associated with the clinical heterogeneity of the disease. Individuals with sickle cell disease are subjected to high levels of oxidative stress. Hydroxyurea (HU) has been used as treatment and it increases the levels of fetal hemoglobin having an action antioxidant. The study aimed to investigate the impact of the use of HU and haplotypes in the oxidative status in patients with sickle cell anemia. Samples from 64 patients treated at the University Hospital Walter Cantídio - HUWC and the control group of 20 individuals without hemoglobinopathies. Patients were stratified into groups: the first one using HU > 1 year, the second using HU ≤ 1 year and the third using of HU (SHU). Confirmation of the diagnosis and analysis of haplotypes were performed by molecular study. The measurements of nitrite (NO2-), malonaldehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione total (GSSG+GSH), oxidized (GSSG) and reduced (GSH) and the ratio GSSG/GSH (glutathione oxidized/reduced) were performed by spectrophotometry. Mean levels of NO2- and MDA were shown to be higher in SHU group, being significant only for MDA (p < 0,05). The assessment of oxidative stress in relation to haplotypes showed that the population without the use of HU levels of NO2- and MDA were similar between groups, with an insignificant increase of GSH-Px in the Bantu/n compared with Benin/n and index GSSG/GSH in the Benin/n compared with Bantu/n. In the population using the HU there was a nonsignificant increase in the levels of NO2- in the Bantu/n compared with Benin/n with similar results between groups of MDA and a significant increase in GSH-Px (p <0.03) in the Benin/n compared with Bantu/n. The results of CAT were similar between groups. The ratio of GSSG/GSH was higher but not significant in the Bantu/n compared to Benin/n. The results of this study support the hypothesis that patients with the sickle cell anemia have a state hiperoxidativo products with high levels of oxidative stress and decreased antioxidant status and that of hydroxyurea had an impact on oxidative stress. However, regarding the impact of the haplotypes in oxidative stress, further studies with a larger sample should be recommended to confirm our results, considering that the group of patients not treated with HU was lower than the group of patients using HU, the which may have interfered in the statistical analysis of results.A anemia falciforme (AF) é uma das alterações genéticas mais comuns em nosso país. Os haplótipos da s-globina estão associados com a heterogeneidade clínica apresentada pela doença. Os portadores de AF são submetidos a elevados níveis de estresse oxidativo. A hidroxiuréia (HU) tem sido utilizada no tratamento por sua ação de elevar os níveis de hemoglobina fetal e ação antioxidante. O estudo teve como objetivo investigar o impacto do uso da HU e dos haplótipos no perfil oxidativo nos pacientes com AF. Foram analisadas amostras de 64 pacientes acompanhados no Hospital Universitário Walter Cantídio - HUWC e do grupo controle de 20 indivíduos sem hemoglobinopatias. Os pacientes foram estratificados em grupos: uso de HU > 1 ano, uso de HU ≤ 1 ano e sem uso de HU (SHU). A confirmação do diagnóstico e a análise dos haplótipos foram realizadas através de estudo molecular. As dosagens do nitrito (NO2-), malonaldeído (MDA), glutationa peroxidase (GSH-Px), catalase (CAT), glutationas total (GSSG+GSH), oxidada (GSSG) e reduzida (GSH) e da relação GSSG/GSH (glutationas oxidada/reduzida) foram realizadas por espectrofotometria. Os níveis médios de NO2-, e MDA mostraram-se mais elevados no grupo SHU, sendo significante apenas para o MDA (p < 0,05). O grupo SHU apresentou atividade média das enzimas CAT (p = 0,031) e GSH-Px (p = 0,036) inferiores aos demais grupos e maior relação GSSG/GSH (p < 0,05). A avaliação do estresse oxidativo em relação aos haplótipos demonstrou que na população sem uso de HU os níveis de NO2- e de MDA foram semelhantes entre os grupos, com um aumento não significante da GSH-Px no grupo Bantu/n em relação ao Benin/n e do índice GSSG/GSH no grupo Benin/n em relação ao Bantu/n. Na população em uso de HU verificou-se um aumento não significante dos níveis de NO2- no grupo Bantu/n em relação ao Benin/n com resultados semelhantes de MDA entre os grupos e um aumento significante da GSH-Px (p<0,03) no grupo Benin/n em relação ao Bantu/n. Os resultados da CAT foram semelhantes entre os grupos. A relação GSSG/GSH foi maior, porém não significante no grupo Bantu/n em relação ao Benin/n. Os resultados do presente estudo reforçam a hipótese de que os pacientes com AF apresentam um estado hiperoxidativo com níveis elevados dos produtos do estresse oxidativo e diminuídos do perfil antioxidante e que a hidroxiuréia teve um impacto sobre o perfil oxidativo. No entanto, em relação ao impacto dos haplótipos no estresse oxidativo, estudos posteriores com uma maior amostragem devem ser recomendados para confirmar nossos resultados, considerando que o grupo de pacientes não tratados com HU foi menor que o grupo de pacientes em uso de HU, o que pode ter interferido na análise estatística dos resultados.Anemia FalciformeEstresse OxidativoHidroxiureiaImpacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciformeImpact of therapy with hydroxyurea and haplotypes in oxidative profile in sickle cell anemiainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2011_dis_bscsantos.pdf2011_dis_bscsantos.pdfapplication/pdf1202381http://repositorio.ufc.br/bitstream/riufc/7053/1/2011_dis_bscsantos.pdf7d35d3c9692b5223a1a2a04d9ccc2ffeMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81786http://repositorio.ufc.br/bitstream/riufc/7053/2/license.txt8c4401d3d14722a7ca2d07c782a1aab3MD52riufc/70532021-02-04 17:26:27.895oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2021-02-04T20:26:27Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme
dc.title.en.pt_BR.fl_str_mv Impact of therapy with hydroxyurea and haplotypes in oxidative profile in sickle cell anemia
title Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme
spellingShingle Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme
Santos, Bruna Stefânia Carvalho dos
Anemia Falciforme
Estresse Oxidativo
Hidroxiureia
title_short Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme
title_full Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme
title_fullStr Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme
title_full_unstemmed Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme
title_sort Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme
author Santos, Bruna Stefânia Carvalho dos
author_facet Santos, Bruna Stefânia Carvalho dos
author_role author
dc.contributor.author.fl_str_mv Santos, Bruna Stefânia Carvalho dos
dc.contributor.advisor1.fl_str_mv Gonçalves, Romélia Pinheiro
contributor_str_mv Gonçalves, Romélia Pinheiro
dc.subject.por.fl_str_mv Anemia Falciforme
Estresse Oxidativo
Hidroxiureia
topic Anemia Falciforme
Estresse Oxidativo
Hidroxiureia
description The sickle cell anemia is one of the most common genetic disorders in our country. The -globin haplotypes are associated with the clinical heterogeneity of the disease. Individuals with sickle cell disease are subjected to high levels of oxidative stress. Hydroxyurea (HU) has been used as treatment and it increases the levels of fetal hemoglobin having an action antioxidant. The study aimed to investigate the impact of the use of HU and haplotypes in the oxidative status in patients with sickle cell anemia. Samples from 64 patients treated at the University Hospital Walter Cantídio - HUWC and the control group of 20 individuals without hemoglobinopathies. Patients were stratified into groups: the first one using HU > 1 year, the second using HU ≤ 1 year and the third using of HU (SHU). Confirmation of the diagnosis and analysis of haplotypes were performed by molecular study. The measurements of nitrite (NO2-), malonaldehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione total (GSSG+GSH), oxidized (GSSG) and reduced (GSH) and the ratio GSSG/GSH (glutathione oxidized/reduced) were performed by spectrophotometry. Mean levels of NO2- and MDA were shown to be higher in SHU group, being significant only for MDA (p < 0,05). The assessment of oxidative stress in relation to haplotypes showed that the population without the use of HU levels of NO2- and MDA were similar between groups, with an insignificant increase of GSH-Px in the Bantu/n compared with Benin/n and index GSSG/GSH in the Benin/n compared with Bantu/n. In the population using the HU there was a nonsignificant increase in the levels of NO2- in the Bantu/n compared with Benin/n with similar results between groups of MDA and a significant increase in GSH-Px (p <0.03) in the Benin/n compared with Bantu/n. The results of CAT were similar between groups. The ratio of GSSG/GSH was higher but not significant in the Bantu/n compared to Benin/n. The results of this study support the hypothesis that patients with the sickle cell anemia have a state hiperoxidativo products with high levels of oxidative stress and decreased antioxidant status and that of hydroxyurea had an impact on oxidative stress. However, regarding the impact of the haplotypes in oxidative stress, further studies with a larger sample should be recommended to confirm our results, considering that the group of patients not treated with HU was lower than the group of patients using HU, the which may have interfered in the statistical analysis of results.
publishDate 2011
dc.date.issued.fl_str_mv 2011
dc.date.accessioned.fl_str_mv 2014-01-06T11:49:18Z
dc.date.available.fl_str_mv 2014-01-06T11:49:18Z
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dc.identifier.citation.fl_str_mv SANTOS, B. S. C. Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme. 2011. 96 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2011.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/7053
identifier_str_mv SANTOS, B. S. C. Impacto da terapia com a hidroxiuréia e dos haplóticos no perfil oxidativo na anemia falciforme. 2011. 96 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2011.
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