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Updated: Aug 8, 2026
The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat
Published on: June 17, 2016
A selective ROCK inhibitor, Y27632, prevents dimethylnitrosamine-induced hepatic fibrosis in rats
S Tada1, H Iwamoto, M Nakamuta
1Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Background:
p160ROCK is a direct Rho target which mediates Rho-induced assembly of focal adhesions and stress fibers. We previously reported that Rho signaling pathways are involved in the activation of hepatic stellate cells (HSC) in vitro. The aim of the present study was to test the hypothesis that an inhibitor specific for p160ROCK (Y27632) could prevent experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in rats.
Methods:
Y27632 was given orally at 30 mg/kg daily for 4 weeks after the first injection of DMN. The degree of fibrosis was evaluated by image analysis and also by measurements of collagen and hydroxyproline content in the liver. The expression of alpha-smooth muscle actin (alpha-SMA) in the liver and in the primary cultured HSC was also evaluated. Semi-quantitative RT-PCR was performed to evaluate the expression of type I collagen mRNA in the liver.
Results:
Y27632 treatment significantly decreased the occurrence of DMN-induced hepatic fibrosis and reduced the collagen and hydroxyproline content and alpha-SMA expression in the liver. The expression of alpha-SMA in HSC was also suppressed in vitro.
Conclusions:
These findings indicate that inhibitors of the Rho-ROCK pathway might be useful therapeutically in hepatic fibrosis.
Insights
Y27632, a p160ROCK inhibitor, effectively prevented dimethylnitrosamine-induced hepatic fibrosis in rats. This suggests Rho-ROCK pathway inhibitors hold therapeutic potential for treating liver fibrosis.
Area of Science:
- Cell Biology
- Biochemistry
- Pharmacology
Background:
- p160ROCK mediates Rho-induced focal adhesion and stress fiber assembly.
- Rho signaling pathways are implicated in hepatic stellate cell (HSC) activation.
- Experimental hepatic fibrosis can be induced by dimethylnitrosamine (DMN).
Purpose of the Study:
- To investigate if a p160ROCK inhibitor (Y27632) can prevent DMN-induced experimental hepatic fibrosis in rats.
- To assess the effect of Y27632 on fibrosis markers in vivo and in vitro.
Main Methods:
- Rats were treated daily with Y27632 (30 mg/kg) orally for 4 weeks post-DMN injection.
- Fibrosis was quantified via image analysis, collagen, and hydroxyproline content.
- Alpha-smooth muscle actin (alpha-SMA) expression and type I collagen mRNA were evaluated in liver tissue and cultured HSC.
Main Results:
- Y27632 treatment significantly reduced DMN-induced hepatic fibrosis.
- Collagen and hydroxyproline content in the liver were decreased by Y27632.
- Alpha-SMA expression was suppressed both in vivo (liver) and in vitro (HSC).
Conclusions:
- Inhibitors targeting the Rho-ROCK pathway demonstrate efficacy in preventing experimental hepatic fibrosis.
- These findings suggest potential therapeutic applications for Rho-ROCK inhibitors in treating liver fibrosis.
