Abstract | AIM: The aim of this study was to examine the preventive effects of ME3738 on hepatic fibrosis induced by bile duct ligation (BDL) in rats. METHODS: RESULTS: Hepatic Hyp content and the area of hepatic fibrosis in BDL rats treated with ME3738 were reduced by 24% and 39% compared with non-treated BDL rats (hepatic Hyp, 9.40 +/- 2.85 vs. 12.39 +/- 3.91 mg/liver; P = 0.036; area of hepatic fibrosis, 13.1 +/- 3.8 vs. 21.5 +/- 10.9; P = 0.045). Furthermore, alpha-SMA-positive cells were significantly reduced by 40% (22.3 +/- 14.8 vs. 37.6 +/- 14.2; P = 0.011), collagen-I mRNA by 83% (6.5 +/- 2.2 vs. 38.3 +/- 9.1; P = 0.002), HO-1 mRNA by 58% (4.13 +/- 1.22 vs. 9.73 +/- 1.80; P = 0.018) and hepatic HO-1 content by 26% (2.13 +/- 0.80 vs. 2.87 +/- 0.19; P = 0.01) following ME3738 treatment. The hepatic expression of TBARS, 4-HNE, 8-OHdG and mRNA levels of TGF-beta1, TIMP-1 and IL-6 in the liver were unchanged by ME3738 treatment. CONCLUSION: Oral ME3738 administration may prevent the progression of hepatic fibrosis in BDL rats through suppression of the activation and collagen synthesis of HSC and, in part, oxidative stress. ME3738 has potential as a therapeutic drug for cholestatic liver fibrosis.
|
Authors | Kazunori Maeda, Masahiko Koda, Tomomitsu Matono, Takaaki Sugihara, Satoru Yamamoto, Masaru Ueki, Yoshikazu Murawaki, Nobuyuki Yamashita, Shoji Nishiyama |
Journal | Hepatology research : the official journal of the Japan Society of Hepatology
(Hepatol Res)
Vol. 38
Issue 7
Pg. 727-35
(Jul 2008)
ISSN: 1386-6346 [Print] Netherlands |
PMID | 18328066
(Publication Type: Journal Article)
|