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Gadoxetic Acid-Enhanced MRI and Sonoelastography: Non-Invasive Assessments of Chemoprevention of Liver Fibrosis in Thioacetamide-Induced Rats with Sho-Saiko-To

Ya-Wen Chen,Meng-Yuan Tsai,H. Pan,H. Tseng,Yu-Ting Hung,Chen-Pin Chou

Published 2014 in PLoS ONE

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.

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