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Table 1 Commonly used animal models in the study of liver fibrosis

From: Potent natural products and herbal medicines for treating liver fibrosis

Model Inducing factor Methodology Characteristics Reference
Bridging fibrosis mice CCl4 Eight-week-old male C57BL/6 J mice are intraperitoneally injected with 0.5-ml/kg body weight CCl4 (1:50 v/v in corn oil) or vehicle (DMSO in corn oil) three times a week for 4 weeks. Calcipotriol (20-μg/kg body weight) is administrated by oral gavage five times a week, commencing 20 days after the first dose of CCl4 Convenient, reproducible, well tolerated, most commonly used model [115]
Alcohol-induced fibrosis Alcohol Alcohol in combination with Western diet is fed to mice intragastrically for 8 weeks Aversion for alcohol, rapid metabolism, difficult to control fibrotic stage [116]
Non-alcoholic steatohepatitis (NASH)-associated fibrosis Methionine and Choline Female C57BL/6 mice are fed a methionine-choline-deficient diet or a methionine-choline-supplemented diet for 10 weeks; the latter control diet is composed of MCD diet supplemented with L-methionine (1.7 g/kg) and choline bitartrate (14.48 g/kg) Similar pathology to human NASH, well characterized, highly reproducible, lack of metabolic context, time consuming [117]
Auto-immune fibrosis Pig serum Male Wistar rats are given intraperitoneal injections of 0.5-ml normal pig serum twice a week for 10 weeks with or without concomitant oral administration of PTX (20 mg/kg) Mimics immunologic component, but lack of stability and time consuming [118]
Biliary fibrosis Bile duct ligation Under methoxyflurane anesthesia, the common bile duct is double-ligated using 4–0 silk after a midline abdominal incision. Sham-operated mice have their common bile duct exposed and manipulated but not ligated Reversible, but highly variable with high mortality rate [119]
CRP-TGF-β1, IL-12p35−/− dnTGFβR transgenic-genetic model Overexpression of TGF-β1 Standard transgenic method TGF-β1 susceptibility, pathophysiological significance, but expensive, and early death with limited application [120]
Mdr2 (Abcb4−/−) transgenic-genetic model Hepatobiliary phosphatidyl-choline Standard transgenic method Hepatic lesions resembling primary sclerosing cholangitis, convenient but expensive [121]