Soy isoflavone delays the progression of thioacetamide-induced liver fibrosis in rats.
OBJECTIVE
Our aim was to investigate the effect of soy isoflavone (SI) on liver fibrosis in a thioacetamide (TAA)-induced rat model.


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).


CONCLUSIONS
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.
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, P.R. China.
Jian-Fang
JF
Li
Bi-Cheng
BC
Chen
Dan-Dan
DD
Lai
Zeng-Rong
ZR
Jia
Roland
R
Andersson
Bo
B
Zhang
Jian-Gao
JG
Yao
Zhen
Z
Yu
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D000077214:Becaplermin; D003094:Collagen / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007529:Isoflavones / Q000008:administration & dosage / Q000627:therapeutic use*; D008099:Liver / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000032:analysis; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013025:Glycine max; D013853:Thioacetamide / Q000008:administration & dosage / Q000633:toxicity; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis; D016896:Treatment Outcome
D000199:Actins; D000077214:Becaplermin; D003094:Collagen; D007529:Isoflavones; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D013853:Thioacetamide; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat