Biphasic effects of ethanol consumption on N,N-dimethylformamide-induced liver injury in mice.
Toxicology
; 506: 153872, 2024 Aug.
Article
em En
| MEDLINE
| ID: mdl-38924947
ABSTRACT
N,N-Dimethylformamide (DMF) is a well-documented occupational hazardous material, which can induce occupational liver injury. The current study was designed to investigate whether ethanol consumption can affect DMF-induced hepatotoxicity and the potential underlying mechanisms involved. We found that a single dose of ethanol (1.25, 2.5, or 5â¯g/kg bw by gavage) significantly repressed the increase in serum alanine transaminase (ALT) and aspartate transaminase (AST) activities and alleviated the liver histopathological changes in mice challenged with 3â¯g/kg DMF. In contrast, long-term moderate drinking (2.5â¯g/kg bw) significantly aggravated the repeated DMF (0.7â¯g/kg bw) exposure-induced increase in the serum ALT and AST activities. Mechanistically, acute ethanol consumption suppressed DMF-induced activation of the NLR family pyrin domain-containing protein 3 (NLRP3) inflammasome, while long-term moderate ethanol consumption promoted hepatocyte apoptosis in the mouse liver. Notably, cytochrome P4502E1 (CYP2E1) protein level and activity in mouse livers were not significantly affected by ethanol per se in the two models. These results confirm that regular drinking can increase the risk of DMF-induced hepatotoxicity, and suggest that DMF-handling workers should avoid consuming ethanol to reduce the risk of DMF-indued liver injury.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Consumo de Bebidas Alcoólicas
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Citocromo P-450 CYP2E1
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Dimetilformamida
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Etanol
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Doença Hepática Induzida por Substâncias e Drogas
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Fígado
Limite:
Animals
Idioma:
En
Revista:
Toxicology
Ano de publicação:
2024
Tipo de documento:
Article