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Title: Nrf2 and Snail-1 in the prevention of experimental liver fibrosis by caffeine
Author: Gordillo-Bastidas, D.
Oceguera-Contreras, E.
Salazar-Montes, A.
Gonzalez-Cuevas, J.
Hernandez-Ortega, L.D.
Armendariz-Borunda, J.
Issue Date: 2013
Abstract: AIM: To determine the molecular mechanisms involved in experimental hepatic fibrosis prevention by caffeine (CFA). METHODS: Liver fibrosis was induced in Wistar rats by intraperitoneal thioacetamide or bile duct ligation and they were concomitantly treated with CFA (15 mg/kg per day). Fibrosis and inflammatory cell infiltrate were evaluated and classified by Knodell index. Inflammatory infiltrate was quantified by immunohistochemistry (anti-CD11b). Gene expression was analyzed by quantitative reverse transcription-polymerase chain reaction for collagen I (Col-1), connective tissue growth factor (CTGF), transforming growth factor β1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1), IL-6, superoxide dismutase (SOD) and catalase (CAT). Activation of Nrf2 and Snail-1 was analyzed by Western-blot. TNF-α expression was proved by enzyme-linked immunosorbant assay, CAT activity was performed by zymography. RESULTS: CFA treatment diminished fibrosis index in treated animals. The Knodell index showed both lower fibrosis and necroinflammation. Expression of profibro-genic genes CTGF, Col-1 and TGF-β1 and proinflam-matory genes TNF-α, I L- 6 and IL- 1 was substantially diminished with CFA treatment with less CD11b positive areas. Significantly lower values of transcriptional factor Snail-1 were detected in CFA treated rats compared with cirrhotic rats without treatment; in contrast Nrf2 was increased in the presence of CFA. Expression of SOD and CAT was greater in animals treated with CFA showing a strong correlation between mRNA expression and enzyme activity. CONCLUSION: Our results suggest that CFA inhibits the transcriptional factor Snail-1, down-regulating profi-brogenic genes, and activates Nrf2 inducing antioxidant enzymes system, preventing inflammation and fibrosis. © 2013 Baishideng Publishing Group Co., Limited. All rights reserved.
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