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Updated: May 16, 2026
The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat
Published on: June 17, 2016
Paeoniflorin regulates macrophage activation in dimethylnitrosamine-induced liver fibrosis in rats
Xiaorong Chen1, Cheng Liu, Yunfei Lu
1Department of Traditional Chinese Medicine, Shanghai Public Health Clinical Center, 2901 Caolang Road, Jin Shan District, Shanghai, 201508, China. xiaorong3chen@yahoo.com.cn
Background:
Macrophages in other organs (e.g. kidneys, lungs, and spleen, et. al) have rarely been reported in the development of liver fibrosis. Therefore, it is important to investigate macrophage activation in the main organs in liver fibrosis. We investigated the potential antifibrogenic effects of paeoniflorin (PF) in a dimethylnitrosamine (DMN)-induced rat model with special focus on inhibiting macrophage activation in the main organs.
Methods:
Rat hepatic fibrosis was induced by treatment with DMN three times weekly over a 4-week period. DMN rats were treated with water, PF, or gadolinium chloride (GdCl3) from the beginning of the 3rd week. The expression of CD68, marker of macrophage, was investigated using immunohistochemical, real-time PCR, and western blot analysis.
Results:
Hepatic hydroxyproline content markedly decreased and histopathology improved in the DMN-PF rats. Expression of desmin and collagen 1 decreased notably in DMN-PF liver. CD68 expression in the liver, spleen and kidney increased markedly after 2 weeks but decreased in DMN-water rats. PF and GdCl3 decreased CD68 expression in the liver and spleen and there was no effect on kidney. CD68 expression in the lung increased gradually during the course of DMN-induced liver fibrosis, and PF inhibited CD68 expression in the lung significantly while GdCl3 increased CD68 markedly. Expression of tumor necrosis factor (TNF-α) was decreased significantly by GdCl3 in the liver, as revealed by real-time PCR analysis. However, GdCl3 could not decrease TNF-α level in the serum by enzyme linked immunosorbent assay (ELISA).
Conclusions:
Macrophage activation was disrupted in the liver, spleen, lung and kidney during development of DMN-induced liver fibrosis. PF administration attenuated DMN-induced liver fibrosis at least in part by regulating macrophage disruption in the main organs.
Insights
Paeoniflorin (PF) may treat liver fibrosis by regulating macrophage activation in the liver, spleen, and lungs. This study investigated PF
Area of Science:
- Hepatology
- Immunology
- Pharmacology
Background:
- Liver fibrosis is a complex condition with macrophage activation playing a key role.
- The involvement of macrophages in organs beyond the liver during fibrosis is not well-understood.
- Paeoniflorin (PF) is investigated for its potential antifibrotic effects, focusing on macrophage modulation.
Purpose of the Study:
- To investigate the antifibrogenic effects of paeoniflorin (PF) in a rat model of liver fibrosis.
- To examine the impact of PF on macrophage activation in the liver and other major organs.
- To understand the role of macrophage disruption in the development of liver fibrosis.
Main Methods:
- Liver fibrosis was induced in rats using dimethylnitrosamine (DMN).
- Rats were treated with water, PF, or gadolinium chloride (GdCl3).
- Macrophage marker CD68 expression was analyzed using immunohistochemistry, real-time PCR, and Western blot.
Main Results:
- PF treatment reduced hepatic hydroxyproline content and improved liver histopathology.
- PF and GdCl3 decreased CD68 expression in the liver and spleen, while PF also inhibited it in the lungs.
- DMN-induced liver fibrosis involved macrophage activation in the liver, spleen, lungs, and kidneys.
Conclusions:
- Paeoniflorin (PF) administration attenuated dimethylnitrosamine (DMN)-induced liver fibrosis.
- PF's antifibrotic effects are partly attributed to regulating macrophage disruption in key organs.
- Macrophage activation is disrupted across multiple organs during liver fibrosis development.
