title: Effects of liposome-encapsulated clodronate on chlorhexidine gluconate-induced peritoneal fibrosis in rats.
abstract: BACKGROUND
  Long-term peritoneal dialysis (PD) causes morphologic and functional changes in the peritoneum that hamper the continuation of PD therapy. Because macrophages play important roles in the development of peritoneal fibrosis and liposome-encapsulated clodronate (LC) induces macrophage apoptosis, we examined the effect of LC on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in rats.
  
  
  METHODS
  Fifty Sprague-Dawley rats were randomly allocated into five groups of 10 receiving intraperitoneal (i.p.) injections (1.5 mL/100 g) of either 0.1% CG (four groups) or vehicle (one group) three times a week. Three of the CG-treated groups also received intravenous injections of clodronate twice a week: 10 mg of LC, 20 mg of LC or 20 mg of unencapsulated clodronate (UC20). Twenty-one days after the first i.p. injection, the rats were sacrificed and the parietal peritoneum was harvested.
  
  
  RESULTS
  The number of peritoneal macrophages in the rats given clodronate was significantly smaller than that in rats not given clodronate (92.0 ± 4.6 cells per field). It was 54.1 ± 3.2 cells per field in the group given 20 mg UC, 43.2 ± 5.2 cells per field in the group given 10 mg LC and 27.2 ± 2.8 cells per field in the group given 20 mg LC. This decrease in macrophage number was paralleled by decreases in peritoneal thickening, in the number of mesothelial cells staining positive for cytokeratin and α-smooth muscle actin and in messenger RNA expression for transforming growth factor-β1 and collagen types I and III.
  
  
  CONCLUSIONS
  These data suggest that macrophages play a critical role in the development of peritoneal fibrosis and that LC may be useful for treating peritoneal fibrosis in PD patients.
authors.affiliation: Department of Nephrology, National Defense Medical College, Tokorozawa, Saitama, Japan.
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Kushiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Oda
authors.forename: Muneharu
authors.initials: M
authors.lastname: Yamada
authors.forename: Keishi
authors.initials: K
authors.lastname: Higashi
authors.forename: Kojiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Naoki
authors.initials: N
authors.lastname: Oshima
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Sakurai
authors.forename: Soichiro
authors.initials: S
authors.lastname: Miura
authors.forename: Hiroo
authors.initials: H
authors.lastname: Kumagai
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D002710:Chlorhexidine / Q000031:analogs & derivatives* / Q000633:toxicity; D004002:Clodronic Acid / Q000627:therapeutic use*; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects*; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D056627:Peritoneal Fibrosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D015415:Biomarkers; D050071:Bone Density Conservation Agents; D008081:Liposomes; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D004002:Clodronic Acid; C010882:chlorhexidine gluconate; D002710:Chlorhexidine