Biliatresone induces cholangiopathy in C57BL/6J neonates.
Sci Rep
; 13(1): 10574, 2023 06 29.
Article
em En
| MEDLINE
| ID: mdl-37386088
ABSTRACT
Exposure to plant toxins or microbiota that are able to digest common food ingredients to toxic structures might be responsible for biliary atresia (BA). An isoflavonoid, biliatresone is known to effectively alter the extrahepatic bile duct (EHBD) development in BALB/c mice. Biliatresone causes a reduction of Glutathione (GSH) levels, SOX17 downregulation and is effectively countered with N-Acetyl-L-cysteine treatment in vitro. Therefore, reversing GSH-loss appears to be a promising treatment target for a translational approach. Since BALB/c mice have been described as sensitive in various models, we evaluated the toxic effect of biliatresone in robust C57BL/6J mice and confirmed its toxicity. Comparison between BALB/c and C57BL/6J mice revealed similarity in the toxic model. Affected neonates exhibited clinical symptoms of BA, such as jaundice, ascites, clay-colored stools, yellow urine and impaired weight gain. The gallbladders of jaundiced neonates were hydropic and EHBD were twisted and enlarged. Serum and histological analysis proved cholestasis. No anomalies were seen in the liver and EHBD of control animals. With our study we join a chain of evidence confirming that biliatresone is an effective agent for cross-lineage targeted alteration of the EHBD system.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Atresia Biliar
/
Colestase
Limite:
Animals
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha