Mizoribine Suppresses the Progression of Experimental Peritoneal Fibrosis in a Rat Model

Takahashi Shunsuke

Taniguchi Yoshihiko

Nakashima Ayumu

Arakawa Tetsuji

Kawai Toru

Doi Shigehiro

Ito Takafumi

Masaki Takao

Kohno Nobuoki

Yorioka Noriaki

Nephron Experimental Nephrology

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.

Macrophage

Mizoribine

Peritoneal dialysis

Peritoneal fibrosis

Experimental peritoneal fibrosis

rat model

Medical sciences [ 490 ]

eng

Karger

Copyright (c) 2009 S. Karger AG, Basel

[ISSN] 1660-2129

[DOI] 10.1159/000213896

[DOI] http://dx.doi.org/10.1159/000213896