Comparative genomic analysis of Fischer F344 rat livers exposed for 90 days to 3-methylfuran or its parental compound furan.
Food Chem Toxicol
; 184: 114426, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38160780
ABSTRACT
Furan is a naturally forming compound found in heat-processed foods such as coffee, canned meats, and jarred baby food. It is concurrently found with analogues including 2-methylfuran (2-MF) and 3-methylfuran (3-MF), and toxicity studies demonstrate all are potent liver toxins. Toxicity studies found 3-MF is more toxic than either furan, or 2-MF. The present analysis assesses the transcriptional response in liver samples taken from male Fischer (F344) rats exposed to furan or 3-MF from 0 to 2.0 and 0-1.0 mg/kg bw/day, respectively, for 90 days. Transcriptional analyses found decreased liver function and fatty acid metabolism are common responses to both furan and 3-MF exposure. Furan liver injury promotes a ductular reaction through Hippo and TGFB signalling, which combined with increased immune response results in ameliorating perturbed bile acid homeostasis in treated rats. Failure to activate these pathways in 3-MF exposed rats and decreased p53 activity leads to cholestasis, and increased toxicity. Finally, BMD analysis indicate many of the most sensitive pathways affected by furan and 3-MF exposure relate to metabolism - malate dehydrogenase and glucose metabolism with BMDLs of 0.03 and 0.01 mg/kg bw/day for furan and 3-MF exposure, respectively, which agrees with BMDLs previously reported for apical and microarray data.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Furanos
/
Fígado
Limite:
Animals
Idioma:
En
Revista:
Food Chem Toxicol
Ano de publicação:
2024
Tipo de documento:
Article