Unraveling DEHP influence on hemoglobin S polymerization in sickle cell disease: Ex vivo, in vitro and in silico analysis.
Toxicol In Vitro
; 98: 105832, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38653437
ABSTRACT
Sickle cell disease (SCD) is a hereditary hemoglobinopathy, caused by a mutation at position 6 of the ß-globin chain and patients are frequently exposed to several blood transfusions in order to maintain physiological function. Transfusion blood bags are composed of PVC and phthalates (as DEHP) are often introduced to the material in order to confer malleability. In this sense, DEHP can easily elute to the blood and cause harmful effects. This study aimed to unravel DEHP effect on SCD patient's hemoglobin function. We found that HbS polymerization using whole erythrocytes is decreased by DEHP in ex vivo experiments and this effect might be mediated by the DEHP-VAL6 interaction, evaluated in silico. Isolated HbS exhibited less polymerization at low DEHP concentrations and increased polymerization rate at higher concentration. When analyzing the propensity to aggregate, HbS is more inclined to aggregate when compared to HbA due to the residue 6 mutation. Circular dichroism showed characteristic hemoglobin peaks for oxygenated HbS that are lost when oxygen is sequestered, and DEHP at higher concentration mildly recovers a peak close to the second hemoglobin one. Finally, by transmission electron microscopy we demonstrated that high DEHP concentration increased polymer formation with a more organized structure. These findings show for the first-time the beneficial effect of low-dose DEHP on HbS polymerization.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hemoglobina Falciforme
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Dietilexilftalato
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Eritrócitos
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Polimerização
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Anemia Falciforme
Limite:
Humans
Idioma:
En
Revista:
Toxicol In Vitro
/
Toxicol. in vitro
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Toxicology in vitro
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Brasil