Korean J Gastroenterol.  2017 Nov;70(5):239-246. 10.4166/kjg.2017.70.5.239.

Effect of Rifaximin on Hepatic Fibrosis in Bile Duct-ligated Rat Model

• Shin SK
• Kwon OS
• Lee JJ
• Park YH
• Choi CS
• Jeong SH
• Choi DJ
• Kim YS
• Kim JH

• KMID: 2398870
• DOI: http://doi.org/10.4166/kjg.2017.70.5.239

Abstract

BACKGROUND/AIMS
The translocation of bacteria and their lipopolysaccharides from the gut can promote fibrosis in cirrhotic patients. The aim of this study was to investigate the effects of rifaximin on hepatic fibrosis in a bile duct-ligated rat model.
METHODS
The bile duct ligation (BDL) was carried out for eight days (acute injury model: sham-operated rats [G1], BDL rats [G2], and BDL rats treated with rifaximin [G3]) or 22 days (chronic injury model: sham-operated rats [G4], BDL rats [G5], and BDL rats treated with rifaximin [G6]). Rifaximin (50 mg/kg/day) was administered daily via gavage after BDL. Liver function, serum tumor necrosis factor-alpha (TNF-α), and hepatic hydroxyproline levels were measured. Moreover, a histological analysis of fibrosis contents was performed using sirius red stain.
RESULTS
In the acute injury model, the liver function and TNF-α level were not improved after the rifaximin treatment. The hydroxyproline levels (µg/g liver tissue) in G1, G2, and G3 were 236.4±103.1, 444.8±114.4, and 312.5±131.6, respectively; and fibrosis contents (%) were 0.22±0.04, 1.64±0.53, and 1.66±0.44, respectively. The rifaximin treatment did not ameliorate acute BDL-induced fibrosis. In the chronic injury model, the hydroxyproline levels in G4, G5, and G6 were 311.5±72.9, 1,110.3±357.9, and 944.3±209.3, respectively; and fibrosis contents (%) were 0.19±0.03, 5.04±0.18, and 4.42±0.68, respectively (G5 vs. G6, p=0.059). The rifaximin treatment marginally ameliorated chronic BDL-induced fibrosis.
CONCLUSIONS
Rifaximin did not reduce inflammation and fibrosis in bile duct-ligated rat model.

Keyword

Liver fibrosis; Bile duct ligation; Rifaximin

MeSH Terms

Animals
Bacteria
Bile Ducts
Bile*
Fibrosis*
Humans
Hydroxyproline
Inflammation
Ligation
Lipopolysaccharides
Liver
Liver Cirrhosis
Models, Animal*
Rats*
Tumor Necrosis Factor-alpha
Hydroxyproline
Lipopolysaccharides
Tumor Necrosis Factor-alpha

Figure

• 

  Fig. 1 Scheme of experimental design. Male adult Sprague-Dawley rats were randomly divided into 6 experimental groups: (A) 3 groups in acute injury model (sham-operated rats [G1], BDL rats [G2], and BDL rats treated with rifaximin [G3]), (B) 3 groups in chronic injury model (sham-operated rats [G4], BDL rats [G5], and BDL rats treated with rifaximin [G6]). The BDL was done for 8 and 22 days for the acute and chronic injury models. Twenty-four hours after BDL or sham operation, water or rifaximin (50 mg/kg/day) was administered daily by gavage. BDL, bile duct ligation.

• 

  Fig. 2 Effects of rifaximin on serum biochemistry in acute (bile duct ligation for 8 days) or chronic (bile duct ligation for 22 days) injury model. (A) Acute injury model. (B) Chronic injury model. Data are expressed as the mean±standard deviation. Sham, sham group; BDL, bile duct ligation operation group; BDL+rifaximin, rifaximin treatment group after bile duct ligation operation; AST, aspartate aminotransferase; ALT, alanine aminotransferase.

• 

  Fig. 3 Effects of rifaximin on serum tumor necrosis factor-alpha level in acute (bile duct ligation for 8 days) or chronic (bile duct ligation for 22 days) injury model. (A) Acute injury model. (B) Chronic injury model. Data are expressed as mean±standard deviation. Sham, sham group; BDL, bile duct ligation operation group; BDL+rifaximin, rifaximin treatment group after bile duct ligation operation; TNF-α, tumor necrosis factor-alpha.

• 

  Fig. 4 Effects of rifaximin on fibrosis contents assessed by hydroxyproline assay in acute (bile duct ligation for 8 days) or chronic (bile duct ligation for 22 days) injury model. (A) Acute injury model. (B) Chronic injury model. Data are representative of at least three independent experiments and are expressed as the mean±standard deviation. Sham, sham group; BDL, bile duct ligation operation group; BDL+rifaximin, rifaximin treatment group after bile duct ligation operation.

• 

  Fig. 5 Effects of rifaximin on liver histology in chronic (bile duct ligation for 22 days) injury model (H&E, ×100). Sham, sham group; BDL, bile duct ligation operation group; BDL+rifaximin, rifaximin treatment group after bile duct ligation operation.

• 

  Fig. 6 Effects of rifaximin on fibrosis contents measured by sirius red staining in acute (bile duct ligation for 8 days) or chronic (bile duct ligation for 22 days) injury model (×100). (A) Acute injury model. (B) Chronic injury model. Percentage of area stained was measured by image analysis from six random fields from each tissue section, and data were pooled to determine the mean. (C) Acute injury model. (D) Chronic injury model. Data are expressed as the mean±standard deviation. Sham, sham group; BDL, bile duct ligation operation group; BDL+rifaximin, rifaximin treatment group after bile duct ligation operation.

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