Paeoniflorin regulates macrophage activation in dimethylnitrosamine-induced liver fibrosis in rats

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 (GdCl(3)) from the beginning of the 3(rd) 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 GdCl(3) 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 GdCl(3) increased CD68 markedly. Expression of tumor necrosis factor (TNF-α) was decreased significantly by GdCl(3) in the liver, as revealed by real-time PCR analysis. However, GdCl(3) 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.