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

Abstract

BACKGROUNDS/AIMS:

It has been reported that tamoxifen may affect hepatoma cell growth in vitro by suppressing transforming growth factor beta-1 (TGF-beta1) expression, suggesting that tamoxifen might also retard fibrogenesis. Thus, we examined whether tamoxifen might suppress TGF-beta1 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-beta1 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-beta1 and TGF-beta 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-beta1 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-beta1 mRNA and type I TGF-beta receptor (TGF-beta RI) mRNA to similar extents.

CONCLUSIONS:

Tamoxifen seems to inhibit the process of hepatic fibrosis dose-dependently by suppressing the transcription of TGF-beta1 and TGF-beta RI in an experimental model of periportal hepatic fibrosis.

• Authors: Soo Hyung Ryu, Young-Hwa Chung, Jae Kyun Lee, Jeong A Kim, Jung Woo Shin, Myoung Kuk Jang, Neung Hwa Park, Han Chu Lee, Yung Sang Lee, Dong Jin Suh
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 29 Issue 2 Pg. 308-14 (Feb 2009) ISSN: 1478-3231 [Electronic] United States
• PMID: 18564211 (Publication Type: Comparative Study, Journal Article)

Chemical References

• DNA Primers
• Propanols
• RNA, Messenger
• Receptors, Transforming Growth Factor beta
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• Tamoxifen
• allyl alcohol
• Collagen

Topics

• Animals
• Collagen (metabolism)
• DNA Primers (genetics)
• Dose-Response Relationship, Drug
• Gene Expression Regulation (drug effects)
• Liver Cirrhosis (chemically induced, drug therapy, pathology)
• Male
• Propanols (toxicity)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Transforming Growth Factor beta (metabolism)
• Statistics, Nonparametric
• Tamoxifen (pharmacology, therapeutic use)
• Transforming Growth Factor beta1 (blood)