Toxic effects of combined treatment of 1,2-dichloroethane and ethanol on mouse brain and the related mechanisms.
J Biochem Mol Toxicol
; 33(5): e22294, 2019 May.
Article
em En
| MEDLINE
| ID: mdl-30664321
ABSTRACT
The aim of this study was to explore the mechanisms of brain damage induced by the combined treatment of mice with 1,2-dichloroethane (1,2-DCE) and ethanol. Mice were divided into control group; 1,2-DCE-intoxicated group; ethanol-treated group; and low-, medium-, and high-dose combined treatment groups. Histological observations along with brain organ coefficients and water content were used to measure the brain damage directly and indirectly. The levels of nonprotein sulfhydryls, malondialdehyde (MDA), and superoxide dismutase activity were used as parameters to evaluate oxidative stress in the brain. Protein and messenger RNA (mRNA) levels of cytochrome P450 2E1 (CYP2E1), zonula occludens-1 (occludin and zo-1), aquaporin-4 (AQP4), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase (HO)-1, and the γ-glutamyl cysteine synthetase catalytic and modulatory subunits (γ-GCSc, GR, and γ-GCSm) in the brain were examined by Western blot analysis and quantitative polymerase chain reaction analysis, respectively. Effects of the combined treatment of 1,2-DCE and ethanol were evaluated by analysis of variance with a factorial design. The results suggested that combined exposure to ethanol and 1,2-DCE synergistically increased CYP2E1 protein and mRNA levels, accelerated the metabolism of ethanol and 1,2-DCE in the brain tissue, induced high production of reactive oxygen species (ROS), and increased MDA levels, thereby damaging the blood-brain barrier and causing obvious pathological changes in brain tissue. However, the increased level of ROS activated the Nrf2 signal transduction pathway, promoting the expression of HO-1 and glutathione-related antioxidant enzymes in the brain to protect the cells from oxidative damage.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Barreira Hematoencefálica
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Regulação da Expressão Gênica
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Espécies Reativas de Oxigênio
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Etanol
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Dicloretos de Etileno
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Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article