Obeticholic acid differentially regulates hepatic injury and inflammation at different stages of D-galactosamine/lipopolysaccharide-evoked acute liver failure.
Eur J Pharmacol
; 850: 150-157, 2019 May 05.
Article
en En
| MEDLINE
| ID: mdl-30772394
ABSTRACT
The farnesoid X receptor (FXR) is a ligand-activated transcription factor that regulates genes involved in bile acid metabolism. Accumulating data demonstrate that FXR has an anti-inflammatory activity. The present study aimed to investigate the effect of obeticholic acid (OCA), a novel synthetic FXR agonist, on D-galactosamine (GalN)/lipopolysaccharide (LPS)-evoked acute liver injury. All mice except controls were intraperitoneally injected with GalN (300â¯mg/kg) plus LPS (2.5⯵g/kg). Some mice were pretreated with OCA (10â¯mg/kg) 48, 24 and 1â¯h before GalN/LPS. As expected, pretreatment with OCA alleviated hepatocyte apoptosis at early and middle stages of GalN/LPS-induced acute liver failure. By contrast, pretreatment with OCA augmented hepatic injury and inflammatory cell infiltration at middle stage of GalN/LPS-induced acute liver failure. Additional experiment found that OCA inhibited hepatic NF-κB activation at early and middle stages of GalN/LPS-induced acute liver failure. Interestingly, OCA inhibited hepatic proinflammatory cytokine tnf-α and il-6 but upregulated hepatic anti-inflammatory cytokine il-10 at early stage of GalN/LPS-induced acute liver failure. By contrast, OCA suppressed hepatic anti-inflammatory cytokine tgf-ß and il-10 at middle stage of GalN/LPS-induced acute liver injury. These results suggest that FXR agonist OCA differentially regulates hepatic injury and inflammation at different stages of GalN/LPS-evoked acute liver failure.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ácido Quenodesoxicólico
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Lipopolisacáridos
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Fallo Hepático Agudo
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Galactosamina
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Hígado
Límite:
Animals
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2019
Tipo del documento:
Article
País de afiliación:
China