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Mizoribine suppresses the progression of experimental peritoneal fibrosis in a rat model
Shunsuke Takahashi1, Yoshihiko Taniguchi, Ayumu Nakashima
1Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi Minami-ku, Hiroshima, Japan.
Background/Aims:
Peritoneal fibrosis is a serious complication of peritoneal dialysis (PD). It has been reported that administration of mizoribine, an effective immunosuppressant, ameliorated renal fibrosis in a rat model of unilateral ureteral obstruction. We therefore examined the effects of mizoribine in an experimental model of peritoneal fibrosis.
Methods:
24 rats were given a daily intraperitoneal injection of chlorhexidine gluconate and ethanol dissolved in saline. The rats were divided into three groups (n = 8 per group) that received either vehicle or mizoribine at a dose of 2 or 8 mg/kg once a day. 28 days after the start of the treatments the rats were sacrificed and peritoneal tissue samples collected. Macrophage infiltration (ED1), myofibroblast accumulation (alpha-smooth muscle actin (SMA)) and expression of type III collagen, transforming growth factor (TGF)-beta and monocyte chemotactic protein-1 (MCP-1) were examined by immunohistochemistry.
Results:
Mizoribine significantly suppressed submesothelial zone thickening and reduced macrophage infiltration. Mizoribine also reduced collagen III(+) area and decreased the number of alpha-SMA(+), TGF-beta(+) and MCP-1(+) cells. The magnitude of the changes observed was dose-dependent.
Conclusion:
The administration of mizoribine prevented the progression of peritoneal fibrosis in this rat model. Mizoribine may represent a novel therapy for peritoneal sclerosis in patients undergoing long-term PD.
Insights
Mizoribine treatment reduced peritoneal fibrosis in rats by decreasing inflammation and collagen deposition. This study suggests mizoribine may be a new therapy for peritoneal sclerosis in patients on peritoneal dialysis.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Peritoneal fibrosis is a severe complication of peritoneal dialysis (PD).
- Mizoribine, an immunosuppressant, has shown efficacy in ameliorating renal fibrosis.
- This study investigates mizoribine's effect on experimental peritoneal fibrosis.
Purpose of the Study:
- To evaluate the therapeutic potential of mizoribine in a rat model of peritoneal fibrosis.
- To assess mizoribine's impact on key fibrotic markers and cellular infiltration.
Main Methods:
- Rats received daily intraperitoneal injections of chlorhexidine gluconate and ethanol.
- Treatment groups received either vehicle or mizoribine (2 or 8 mg/kg) daily for 28 days.
- Immunohistochemistry was used to analyze macrophage infiltration, myofibroblast accumulation, and expression of collagen III, TGF-beta, and MCP-1.
Main Results:
- Mizoribine significantly reduced submesothelial thickening and macrophage infiltration.
- The drug decreased collagen III-positive areas and the number of alpha-SMA, TGF-beta, and MCP-1 positive cells.
- These effects were dose-dependent.
Conclusions:
- Mizoribine administration effectively prevented the progression of peritoneal fibrosis in the experimental model.
- Mizoribine shows promise as a novel therapeutic agent for peritoneal sclerosis in patients undergoing long-term PD.