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

Korean J Gastroenterol. 2017 Nov 25;70(5):239-246. doi: 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.

Keywords: Bile duct ligation; Liver fibrosis; Rifaximin.

MeSH terms

  • Acute Disease
  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Bile Ducts / surgery*
  • Bilirubin / blood
  • Chronic Disease
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Hydroxyproline / metabolism
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / pathology
  • Male
  • Nucleic Acid Synthesis Inhibitors / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Rifamycins / therapeutic use*
  • Rifaximin
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Nucleic Acid Synthesis Inhibitors
  • Rifamycins
  • Tumor Necrosis Factor-alpha
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Rifaximin
  • Bilirubin
  • Hydroxyproline