Fisetin alleviates thioacetamide-induced hepatic fibrosis in rats by inhibiting Wnt/ß-catenin signaling pathway.
Immunopharmacol Immunotoxicol
; 44(3): 355-366, 2022 Jun.
Article
en En
| MEDLINE
| ID: mdl-35255766
ABSTRACT
BACKGROUND:
Liver fibrosis is a chronic wound-healing response to liver injury of various origins and represents a major health problem.OBJECTIVE:
The current study endeavored to investigate the repressing effect of fisetin on hepatic fibrosis induced by thioacetamide (TAA) in rats. MATERIALS ANDMETHODS:
Rats were injected with TAA (200 mg/kg) intraperitoneally twice per week for 6 weeks to induce liver fibrosis. Fisetin (50 and 100 mg/kg/day) or silymarin (50 mg/kg/day) were given orally on a daily basis along with TAA. Liver function parameters, oxidative stress, inflammatory and fibrogenic biomarkers as well as wnt3a, ß-catenin, glycogen synthase kinase 3 (GSK-3ß) and cyclin D1 were estimated. Histoapthological and immunohistochemical examinations were performed.RESULTS:
Fisetin restored normal liver functions, increased reduced glutathione (GSH) level and decreased malondialdehyde (MDA), as well as inflammatory biomarkers including; tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, it lessened transforming growth factor ß1 (TGF-ß1), collagen I and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels as well as elevated matrix metalloproteinase-9 (MMP-9) hepatic content. Furthermore, fisetin significantly suppressed wnt3a gene expression associated with decreased ß-catenin and increased GSK-3ß levels. Moreover, fisetin decreased the progress of histologic hepatic fibroplasia and diminished hepatic expression of α-SMA and cyclin D1.CONCLUSION:
Fisetin curbed liver fibrosis and exhibited superior activity over silymarin through inhibition of hepatic stellate cells (HSCs) activation and proliferation via suppressing the Wnt/ß-catenin pathway, modulating MMP-9 and TIMP-1, and inhibiting multiple profibrogenic factors, besides its antioxidant and anti-inflammatory effects. Therefore, fisetin is a promising therapeutic candidate for hepatic fibrosis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Silimarina
/
Tioacetamida
Límite:
Animals
Idioma:
En
Revista:
Immunopharmacol Immunotoxicol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
/
TOXICOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Egipto