Soy isoflavone delays the progression of thioacetamide-induced liver fibrosis in rats

Jian-Fang Liab, Bi-Cheng Chenc, Dan-Dan Laid, Zeng-Rong Jiaa, Roland Anderssone, Bo Zhanga, Jian-Gao Yaoa & Zhen Yu*aa Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, P.R. Chinab Department of General Surgery, The First People's Hospital of Xiaoshan, Hangzhou, P.R. Chinac Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, P.R. Chinad Department of Cardiovasology, The First People's Hospital of Xiaoshan, Hangzhou, P.R. Chinae Department of Surgery, Clinical Sciences Lund, Lund University and Lund University Hospital, SwedenCorrespondence: Zhen Yu, MD, PhD, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical College, 2 Fuxue Lane, Wenzhou 325000, Zhejiang, PR China. yuzhen0577@gmail.com *Co-first coauthors, these authors contributed equally to this work.Abstract Objective. Our aim was to investigate the effect of soy isoflavone (SI) on liver fibrosis in a thioacetamide (TAA)-induced rat model. Materials and methods. Twenty-eight rats were assigned to four groups: sham group, fibrosis group, low-dose treatment group (LDg) and high-dose treatment group (HDg). SI (90 or 270 mg/kg) was administered daily during the model development by TAA. Standard liver tests, platelet derived growth factor-BB (PDGF-BB) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured. The expression of collagen, α-smooth muscle actin (α-SMA) and transforming growth factor-β1 (TGF-β1) in liver tissue was determined. Electron microscopy was used to perform ultrastructural analysis of the livers. Results. Hepatic fibrosis was induced by 8 weeks of TAA administration. However, following the administration of SI, collagen staining significantly declined as compared with the fibrosis group (p < 0.01). Less collagen fibers around the hepatic stellate cells (HSCs) were observed in HDg as compared to the fibrosis group and LDg. There was no significant difference in standard liver tests between the fibrosis group and the two treatment groups. The levels of PDGF-BB and TIMP-1 in the two SI-treated groups were significantly lower than in the fibrosis group (p < 0.01). The expression of α-SMA and TGF-β1 in HDg was less than that in the fibrosis group and LDg (p < 0.01). Conclusion. Administration of a high dose of SI resulted in an obvious inhibitory effect on liver fibrosis induced by TAA in rats. One hypothesis is that the effect may be related to the inhibition of HSC activation and proliferation.