Mizoribine suppresses the progression of experimental peritoneal fibrosis in a rat model.
OBJECTIVE
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.


CONCLUSIONS
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.
Takahashi
Shunsuke
S
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi Minami-ku, Hiroshima, Japan.
Taniguchi
Yoshihiko
Y
Nakashima
Ayumu
A
Arakawa
Tetsuji
T
Kawai
Toru
T
Doi
Shigehiro
S
Ito
Takafumi
T
Masaki
Takao
T
Kohno
Nobuoki
N
Yorioka
Noriaki
N
D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000378:metabolism; D002710:Chlorhexidine / Q000009:adverse effects / Q000031:analogs & derivatives; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology; D010532:Peritoneal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010537:Peritoneum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012263:Ribonucleosides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000199:Actins; D018932:Chemokine CCL2; D002710:Chlorhexidine; D024061:Collagen Type III; D007166:Immunosuppressive Agents; D012263:Ribonucleosides; D016212:Transforming Growth Factor beta; C491766:Ccl2 protein, rat; C498862:Acta2 protein, rat; C010052:mizoribine; C010882:chlorhexidine gluconate