title: Mizoribine suppresses the progression of experimental peritoneal fibrosis in a rat model.
abstract: 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.
authors.affiliation: Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi Minami-ku, Hiroshima, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Takahashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Arakawa
authors.forename: Toru
authors.initials: T
authors.lastname: Kawai
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Doi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Ito
authors.forename: Takao
authors.initials: T
authors.lastname: Masaki
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.forename: Noriaki
authors.initials: N
authors.lastname: Yorioka
mesh_terms: 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
chemical_list: 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