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Impaired antioxidant capacity causes a disruption of metabolic homeostasis in sickle erythrocytes.
Chaves, Nayara Alves; Alegria, Thiago Geronimo Pires; Dantas, Lucas Souza; Netto, Luis Eduardo Soares; Miyamoto, Sayuri; Bonini Domingos, Claudia Regina; da Silva, Danilo Grünig Humberto.
Afiliación
  • Chaves NA; UNESP- Sao Paulo State University, Department of Biology, Sao Paulo, Brazil.
  • Alegria TGP; USP - University of Sao Paulo, Institute of Biosciences, Department of Genetics and Evolutionary Biology, Sao Paulo, Brazil.
  • Dantas LS; USP - University of Sao Paulo, Institute of Chemistry, Department of Biochemistry, Sao Paulo, Brazil.
  • Netto LES; USP - University of Sao Paulo, Institute of Biosciences, Department of Genetics and Evolutionary Biology, Sao Paulo, Brazil.
  • Miyamoto S; USP - University of Sao Paulo, Institute of Chemistry, Department of Biochemistry, Sao Paulo, Brazil.
  • Bonini Domingos CR; UNESP- Sao Paulo State University, Department of Biology, Sao Paulo, Brazil.
  • da Silva DGH; UNESP - Sao Paulo State University, Department of Chemistry and Environmental Sciences, 131 Sao Paulo, Brazil. Electronic address: dangrunig@gmail.com.
Free Radic Biol Med ; 141: 34-46, 2019 09.
Article en En | MEDLINE | ID: mdl-31163255
This study examined particularly relevant redox pathways such as glycolysis, pentose phosphate pathway (PPP), metHb reductase and nucleotide metabolism, in order to better address how sickle cells deal with redox metabolism disruption. We also investigated the generation of specific oxidative lesions, and the levels of an unexplored antioxidant that could act as a candidate biomarker for oxidative status in sickle cell anemia (SCA). We adopted rigorous exclusion criteria to obtain the studied groups, which were composed by 10 subjects without hemoglobinopathies and 10 SCA patients. We confirmed that sickle cells overwhelm the antioxidant defense system, leading to an impaired antioxidant capacity that significantly contributed to the increase in cholesterol oxidation (ChAld) and hemolysis. Among the antioxidants evaluated, ergothioneine levels decreased in SCA (two-fold). We found strong correlations of ergothioneine levels with other erythrocyte metabolism markers, suggesting its use as an antioxidant therapy alternative for SCA treatment. Moreover, we found higher activities of MetHb reductase, AChE, G6PDH, HXK, and LDH, as well as levels of NADPH, ATP and hypoxanthine in sickle cells. On this basis, we conclude that impaired antioxidant capacity leaves to a loss of glycolysis and PPP shifting mechanism control and further homeostasis rupture, contributing to a decreased lifespan of sickle cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Eritrocitos / Homeostasis / Anemia de Células Falciformes / Antioxidantes Tipo de estudio: Etiology_studies / Observational_studies Límite: Adult / Female / Humans / Male País/Región como asunto: America do sul / Brasil Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Eritrocitos / Homeostasis / Anemia de Células Falciformes / Antioxidantes Tipo de estudio: Etiology_studies / Observational_studies Límite: Adult / Female / Humans / Male País/Región como asunto: America do sul / Brasil Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos