Gadoxetic acid-enhanced MRI and sonoelastography: non-invasive assessments of chemoprevention of liver fibrosis in thioacetamide-induced rats with Sho-Saiko-To

PLoS One. 2014 Dec 9;9(12):e114756. doi: 10.1371/journal.pone.0114756. eCollection 2014.

Abstract

Background: This study aimed to compare the performance of gadoxetic acid -enhanced magnetic resonance imaging (MRI) and sonoelastography in evaluating chemopreventive effects of Sho-Saiko-To (SST) in thioacetamide (TAA)-induced early liver fibrosis in rats.

Materials and methods: Ten of Sprague-Dawley rats receiving TAA (200 mg/kg of body weight) intraperitoneal injection were divided into three groups: Group 1 (TAA only, n = 3), Group 2 (TAA +0.25 g/kg SST, n = 4) and Group 3 (TAA+1 g/kg SST, n = 3). Core needle liver biopsy at week 2 and liver specimens after sacrifice at week 6 confirmed liver fibrosis using histological examinations, including Sirius red staining, Ishak and Metavir scoring systems. Gadoxetic acid-enhanced MRI and shear-wave sonoelastography were employed to evaluate liver fibrosis. The expression of hepatic transporter organic anion transporter 1 (Oatp1), multidrug-resistant protein 2 (Mrp2) and alpha-smooth muscle actin (α-Sma) were also analyzed in each group by immunohistochemistry (IHC) and Western blot.

Results: According to histological grading by Sirius red staining, Ishak scores of liver fibrosis in Groups 1, 2 and 3 were 3, 2 and 1, respectively. As shown in gadoxetic acid-enhanced MRI, the ratio of relative enhancement was significantly lower in Group 1 (1.87 ± 0.21) than in Group 2 of low-dose (2.82 ± 0.25) and Group 3 of high-dose (2.72 ± 0.12) SST treatment at 10 minutes after gadoxetic acid intravenous injection (p < 0.05). Sonoelastography showed that the mean difference before and after experiments in Groups 1, 2 and 3 were 4.66 ± 0.1, 4.4 ± 0.57 and 3 ± 0.4 KPa (p < 0.1), respectively. Chemopreventive effects of SST reduced the Mrp2 protein level (p < 0.01) but not Oatp1 and α-Sma levels.

Conclusion: Sonoelastography and gadoxetic acid-enhanced MRI could monitor the treatment effect of SST in an animal model of early hepatic fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Contrast Media / pharmacokinetics
  • Disease Models, Animal
  • Drugs, Chinese Herbal / chemistry*
  • Elasticity Imaging Techniques / methods*
  • Gadolinium DTPA / pharmacokinetics*
  • Immunoenzyme Techniques
  • Liver Cirrhosis / chemically induced
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / prevention & control*
  • Liver Function Tests
  • Magnetic Resonance Imaging / methods*
  • Male
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Thioacetamide / toxicity*
  • Tissue Distribution

Substances

  • Biomarkers
  • Contrast Media
  • Drugs, Chinese Herbal
  • Plant Extracts
  • gadolinium ethoxybenzyl DTPA
  • shosaiko-to
  • Thioacetamide
  • Gadolinium DTPA

Grants and funding

This study was supported by grants NSC 99-2314-B-075B-006-MY3, NSC 102-2320-B-400-004, NHRI CA-103-PP-03 from Ministry of Science and Technology and National Health Research Institutes, Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.