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Antifibrogenic effects of tamoxifen in a rat model of periportal hepatic fibrosis
Author(s) -
Ryu Soo Hyung,
Chung YoungHwa,
Lee Jae Kyun,
Kim Jeong A.,
Shin Jung Woo,
Jang Myoung Kuk,
Park Neung Hwa,
Lee Han Chu,
Lee Yung Sang,
Suh Dong Jin
Publication year - 2009
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2008.01811.x
Subject(s) - tamoxifen , endocrinology , medicine , fibrosis , hepatic fibrosis , hepatic stellate cell , in vivo , transforming growth factor , receptor , messenger rna , chemistry , biology , cancer , breast cancer , microbiology and biotechnology , biochemistry , gene
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.