Antifibrogenic effects of tamoxifen in a rat model of periportal hepatic fibrosis
Article first published online: 28 JUN 2008
© 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd
Volume 29, Issue 2, pages 308–314, February 2009
How to Cite
Ryu, S. H., Chung, Y.-H., Lee, J. K., Kim, J. A., Shin, J. W., Jang, M. K., Park, N. H., Lee, H. C., Lee, Y. S. and Suh, D. J. (2009), Antifibrogenic effects of tamoxifen in a rat model of periportal hepatic fibrosis. Liver International, 29: 308–314. doi: 10.1111/j.1478-3231.2008.01811.x
- Issue published online: 6 JAN 2009
- Article first published online: 28 JUN 2008
- Received 3 May 2008Accepted 14 May 2008
- hepatic fibrosis;
- Type I TGF-β receptor
Backgrounds/Aims: It has been reported that tamoxifen may affect hepatoma cell growth in vitro by suppressing transforming growth factor β-1 (TGF-β1) expression, suggesting that tamoxifen might also retard fibrogenesis. Thus, we examined whether tamoxifen might suppress TGF-β1 expression and consequently inhibit the process of hepatic fibrosis in vivo.
Methods: To induce periportal hepatic fibrosis, 50 male adult Sprague–Dawley rats were injected with 0.62 mmol/kg of allyl alcohol, intraperitoneally, twice a week for 8 weeks. Hepatic fibrosis scores, intrahepatic collagen levels and plasma TGF-β1 expression levels were evaluated in three groups of 10 rats orally administered tamoxifen at 1, 5 and 10 mg/kg, respectively, and in 20 controls. Messenger RNAs (mRNAs) encoding TGF-β1 and TGF-β receptors in liver tissue were semiquantified using reverse transcriptase polymerase chain reaction.
Results: Hepatic fibrosis scores decreased progressively as the dose of tamoxifen increased, resulting in a significant change in rats treated with tamoxifen at 10 mg/kg compared with controls (P=0.018). Intrahepatic collagen content was significantly less in the group treated with tamoxifen at 10 mg/kg compared with the control (P=0.045). Plasma TGF-β1 levels were also significantly lower in rats treated with tamoxifen at 10 mg/kg compared with controls (P=0.007). All three concentrations of tamoxifen tested decreased the expression levels of hepatic TGF-β1 mRNA and type I TGF-β receptor (TGF-β RI) mRNA to similar extents.
Conclusions: Tamoxifen seems to inhibit the process of hepatic fibrosis dose-dependently by suppressing the transcription of TGF-β1 and TGF-β RI in an experimental model of periportal hepatic fibrosis.