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Takahashi S, Taniguchi Y, Nakashima A, Arakawa T, Kawai T, Doi S, Ito T, Masaki T, Kohno N, Yorioka N: Mizoribine suppresses the progression of experimental peritoneal fibrosis in a rat model. Nephron Exp Nephrol. 2009;112(2):e59-69. Epub 2009 Apr 23.
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. |
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