title: Effect of sirolimus on the regression of peritoneal sclerosis in an experimental rat model.
abstract: OBJECTIVE
  Immunosuppressive and anti-inflammatory agents have recently become increasingly popular in the treatment of encapsulating peritoneal sclerosis (EPS). The aim of our study was to investigate the effects of sirolimus on EPS in a rat model.
  
  
  METHODS
  We separated 32 non-uremic rats into four groups: 1 control group, 2 ml isotonic saline injected IP daily for 3 weeks; 2 chlorhexidine gluconate (CG) group, 2 ml 0,1 % CG and 15 % ethanol dissolved in saline injected IP daily for 3 weeks; 3 resting group, CG (weeks 0-3) plus peritoneal rest (weeks 3-6); 4 sirolimus group, CG (weeks 0-3), plus 0.2 ml (1 mg/ml) sirolimus (weeks 3-6). Pathological samples were examined by using hematoxylin eosin (HE) and Masson's trichrome stains. Peritoneal thickness, fibrosis, vascular changes, and inflammation were evaluated by light microscopy. Finally, tissue metalloproteinase (MMP)-2 levels were measured by enzyme-linked immunoassay.
  
  
  RESULTS
  In the CG group, there was a significant increase in peritoneal thickness, inflammatory activity, and fibrosis score compared to the control group (p < 0.05). We also observed a lower fibrosis score and less peritoneal thickening in the sirolimus group compared to the resting and CG groups (p < 0.05). There was no difference in histopathologic findings, except for the inflammatory activity in the sirolimus group, compared to the control group. Although the CG group had higher tissue MMP-2 levels than the control group, the tissue MMP-2 levels were not significantly different from the other groups.
  
  
  CONCLUSIONS
  Sirolimus has a beneficial effect on peritoneal fibrosis induced by CG. This suggests that sirolimus may have therapeutic value in the management of EPS.
authors.affiliation: Department of Nephrology, Ankara Education and Research Hospital, Ankara, Turkey. mevlutceri@gmail.com
authors.forename: Mevlut
authors.initials: M
authors.lastname: Ceri
authors.forename: Selman
authors.initials: S
authors.lastname: Unverdi
authors.forename: Mehmet
authors.initials: M
authors.lastname: Dogan
authors.forename: Hatice
authors.initials: H
authors.lastname: Unverdi
authors.forename: Gokhan
authors.initials: G
authors.lastname: Karaca
authors.forename: Gulay
authors.initials: G
authors.lastname: Kocak
authors.forename: Ilhan
authors.initials: I
authors.lastname: Kurultak
authors.forename: Erdem
authors.initials: E
authors.lastname: Akbal
authors.forename: Murat
authors.initials: M
authors.lastname: Can
authors.forename: Murat
authors.initials: M
authors.lastname: Duranay
mesh_terms: D000818:Animals; D002710:Chlorhexidine / Q000031:analogs & derivatives; D005260:Female; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D010530:Peritoneal Dialysis / Q000009:adverse effects; D056627:Peritoneal Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000627:therapeutic use*; D018709:Statistics, Nonparametric
chemical_list: D007166:Immunosuppressive Agents; D020778:Matrix Metalloproteinase 2; C010882:chlorhexidine gluconate; D002710:Chlorhexidine; D020123:Sirolimus