Journal
JOURNAL OF NUTRITION
Volume 141, Issue 7, Pages 1299-1305Publisher
OXFORD UNIV PRESS
DOI: 10.3945/jn.111.140954
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Funding
- Brazilian agencies Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
- Fundo de Incentivo a Pesquisa e Eventos of the Hospital de Clinicas of Porto Alegre (HCPA)
- Laboratory of Experimental Hepatology-Physiology (HCPA/UFRGS) of the Federal University do Rio Grande do Sul (UFRGS)
- Programa Hispano-Brasileno de Cooperacion Interuniversitaria [HB2006-0031-PC]
- Institut de Salud Carlos III
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The hepatic wound-healing response to chronic noxious stimuli may lead to liver fibrosis, a key feature of the preneoplastic cirrhotic liver. Fibrogenic cells activate in response to a variety of cytokines, growth factors, and inflammatory mediators. The involvement of members of the epidermal growth factor family in this process has been suggested. Amphiregulin is an epidermal growth factor receptor (EGFR) ligand specifically induced upon liver injury. We investigated the effects of quercetin on the amphiregulin/EGFR signal and on the activation of downstream pathways leading to cell growth. Rats were divided into 4 groups (8 rats/group): rats subjected to common bile duct ligation (CBDL), Sham (rats subjected to simulated CBDL), quercetin-treated sham, and quercetin-treated CBDL (CBDL-Q). Quercetin (50 mg/kg i.p. injection) was administered daily for 2 wk starting on d 14 after surgery. Overexpression of amphiregulin, EGFR, TNF alpha, IL-6, TGF beta, platelet-derived growth factor (PDGF), extracellular regulated kinase, protein kinase B (Akt), cycloxygenase (COX)-2, and glioma-associated oncogenes (GLI)-1 and-2 were observed in liver of CBDL rats after 4 wk of bile duct ligation. CBDL-Q rats had a significantly diminished expression of amphiregulin and EGFR compared with untreated CBDL rats. Furthermore, mRNA levels of TNF alpha, IL-6, TGF beta, and PDGF and the protein content of COX-2, GLI-1, and GLI-2 were significantly lower in CBDL-Q rats than in untreated CBDL rats. The findings indicate that quercetin ameliorated activation of survival pathways and downregulated the expression of genes related to inflammation and precancerous conditions. Suppression of amphiregulin/EGFR signals may contribute to this effect. J. Nutr. 141: 1299-1305, 2011.
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