Fenofibrate reverses liver fibrosis in cholestatic mice induced by alpha-naphthylisothiocyanate
Cholestatic liver fibrosis occurs in liver injuries accompanied by inflammation, which develops into cirrhosis if not effectively treated in early stage. The aim of the study is to explore the effect of fenofibrate on liver fibrosis in chronic cholestatic mice. In this study, wild-type
(WT) and Pparα-null (KO) mice were dosed alpha-naphthylisothiocyanate (ANIT) diet to induce chronic cholestasis. Induced liver fibrosis was determined by pathological biomarkers. Then fenofibrate 25 mg/kg was orally administrated to mice twice/day for 14 days. Serum and liver samples
were collected for analysis of biochemistry and fibrosis. In WT mice, cholestatic biomarkers were increased by 5–8-fold and the expression of tissue inhibitors of metalloproteinases 1 (TIMP-1), Monocyte chemoattractant protein 1 (MCP-1), Collagen protein I (Collagen I) was increased
by more than 10-fold. Fenofibrate significantly downgraded the biochemical and fibrotic biomarkers. In Western blot analysis, levels of collagenI and alpha-smooth muscle actin (α-SMA) were strongly inhibited by fenofibrate. In KO mice, liver fibrosis was induced successfully, but no
improvement after fenofibrate treatment was observed. These data showed low-dose fenofibrate reverses cholestatic liver fibrosis in WT mice but not in KO mice, suggesting the dependence of therapeutic action on peroxisome proliferator-activated receptor alpha (PPARα). The study offers
an additional therapeutic strategy for cholestatic liver fibrosis in practice.
Document Type: Research Article
Affiliations: 1: Department of Pharmacology, Medical School of Ningbo University, Ningbo, Zhejiang, P. R. China 2: Department of Health Management, Ningbo College of Health Sciences, Ningbo, Zhejiang, P. R. China 3: Department of Pharmacology, Medical School of Ningbo University, Ningbo, Zhejiang, P. R. China;, Email: [email protected]
Publication date: 01 February 2021
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