Estresse oxidativo em doentes falciformes: influência dos haplótipos e udo de medicação específica
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Data
2010-02-23
Autores
Belini Júnior, Édis [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A causa principal da doença falciforme (DF) é uma mutação pontual no gene β globina que codifica uma hemoglobina (Hb) com características diferentes da Hb normal, denominada de Hb S. Sua fisiopatologia multifacetada envolve múltiplas alterações nos eritrócitos falcêmicos, episódios vaso-oclusivos, hemólise, ativação de mediadores inflamatórios, disfunção das células endoteliais e estresse oxidativo. Com isso, há uma diminuição do fluxo sanguíneo e obstrução da microcirculação acarretando aos portadores, anemia, crises de dor e insuficiência de múltiplos órgãos. Visto que o excesso de espécies reativas de oxigênio é citotóxico modificando vários mecanismos celulares e, consequentemente, ocasionando danos aos órgãos, pretendeu-se avaliar a capacidade antioxidante e o estresse oxidativo em DF, correlacionando com os genótipos da DF, haplótipos do cluster β globina e o uso de medicação específica. Em um estudo longitudinal, foram avaliadas, para o Tempo 1 (T1) de análise, 69 amostras de sangue e, para o Tempo 2 (T2), 55 amostras de DF do Hemocentro de São José do Rio Preto (SJRP) e do Hemocentro da Santa Casa de São Paulo (SP). As amostras foram submetidas a testes eletroforéticos, cromatográficos e moleculares para a identificação dos genótipos da DF e haplótipos do cluster , bem como dosagens bioquímicas para determinação das espécies reativas ao ácido tiobarbitúrico (TBARS) e da capacidade antioxidante em equivalência ao Trolox (TEAC). Por meio da caracterização genotípica da DF, encontramos um maior número de Hb SS, tanto em SP quanto em SJRP. Houve maior frequência da interação Hb S/Beta talassemia em SJRP (10,9%) com as mutações características de países mediterrâneos como a CD39 e IVS-I-110. O haplótipo Bantu foi mais frequente nos dois grupos (60,6%); o haplótipo II esteve associado à mutação...
The main cause of sickle cell disease (SCD) is a single β-globin gene mutation that encodes a hemoglobin (Hb) with different characteristics from normal Hb, called Hb S. This disease is characterized by presenting a multifaceted pathophysiology which involves multiple changes in sickle erythrocytes, vaso-occlusive episodes, hemolysis, inflammatory mediators activation, oxidative stress and endothelical cells dysfunction. Thereby, there is a decrease in blood flow and obstruction of the microcirculation leading the patients to anemia, pain crises and failure of multiple organs. Since the excess of reactive oxygen species is cytotoxic, modifying various cellular mechanisms, and thus, causing damage to organs, the aim of this work was to assess the antioxidant capacity and oxidative stress in SCD, correlating with SCD genotypes, cluster β-globin haplotypes and specific medication. In a longitudinal study were evaluated for the T1: 69 samples of peripheral blood, and for the T2: 55 samples of the SCD patients from Blood Center of the São José do Rio Preto (SJRP) and the Blood Center of the Santa Casa Medical School of São Paulo (SP). We performed electrophoretics, chromatographic and molecular assays for SCD genotypes and cluster β-globin identification, such as biochemical measurements for the determination of thiobarbituric acid reactive species (TBARS) and Trolox equivalence antioxidant capacity (TEAC). Through SCD genetic characterization, we found a greater number of Hb SS in both SP and in SJRP. There was a higher frequency of interaction Hb S/Beta-thalassemia in SJRP (10.9%) with typical mutation of Mediterranean countries such as CD39 and IVS-I -110. The Bantu haplotype was more frequent in both groups (60.6%); the haplotype II was associated with CD39 mutation and the haplotype I with the IVS-I-110. We found a patient with Cameroon haplotype, rare in the Brasilian... (Complete abstract click electronic access below)
The main cause of sickle cell disease (SCD) is a single β-globin gene mutation that encodes a hemoglobin (Hb) with different characteristics from normal Hb, called Hb S. This disease is characterized by presenting a multifaceted pathophysiology which involves multiple changes in sickle erythrocytes, vaso-occlusive episodes, hemolysis, inflammatory mediators activation, oxidative stress and endothelical cells dysfunction. Thereby, there is a decrease in blood flow and obstruction of the microcirculation leading the patients to anemia, pain crises and failure of multiple organs. Since the excess of reactive oxygen species is cytotoxic, modifying various cellular mechanisms, and thus, causing damage to organs, the aim of this work was to assess the antioxidant capacity and oxidative stress in SCD, correlating with SCD genotypes, cluster β-globin haplotypes and specific medication. In a longitudinal study were evaluated for the T1: 69 samples of peripheral blood, and for the T2: 55 samples of the SCD patients from Blood Center of the São José do Rio Preto (SJRP) and the Blood Center of the Santa Casa Medical School of São Paulo (SP). We performed electrophoretics, chromatographic and molecular assays for SCD genotypes and cluster β-globin identification, such as biochemical measurements for the determination of thiobarbituric acid reactive species (TBARS) and Trolox equivalence antioxidant capacity (TEAC). Through SCD genetic characterization, we found a greater number of Hb SS in both SP and in SJRP. There was a higher frequency of interaction Hb S/Beta-thalassemia in SJRP (10.9%) with typical mutation of Mediterranean countries such as CD39 and IVS-I -110. The Bantu haplotype was more frequent in both groups (60.6%); the haplotype II was associated with CD39 mutation and the haplotype I with the IVS-I-110. We found a patient with Cameroon haplotype, rare in the Brasilian... (Complete abstract click electronic access below)
Descrição
Palavras-chave
Sangue - Doenças, Hemoglobinopatia, Anemia falciforme, Doença falciforme, Estresse oxidativo, Hidroxiureia, Deferasirox, Sickle cell disease, Hydroxyurea, Deferasirox
Como citar
BELINI JÚNIOR, Édis. Estresse oxidativo em doentes falciformes: influência dos haplótipos e udo de medicação específica. 2010. 164 f. Dissertação (mestrado) - Universidade Estadual Paulista, Instituto de Biociências, Letras e Ciências Exatas, 2010.