Antifibrogenic effects of tamoxifen in a rat model of periportal hepatic fibrosis


Young-Hwa Chung, MD, Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Poongnap-dong Songpa-ku, 138-736, Seoul, Republic of Korea
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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.