title: Role of tyrosine kinase inhibition with imatinib in an encapsulating peritoneal sclerosis rat model.
abstract: BACKGROUND
  Encapsulating peritoneal sclerosis (EPS) is characterized by neovascularization, increased inflammation, and interstitial fibrosis of the peritoneum. We investigated the effects of imatinib on the peritoneal membrane in an experimental EPS model.
  
  
  METHODS
  We separated 24 non-uremic Wistar rats into four groups: the control group which was injected with 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks, the CG group which was injected with chlorhexidine gluconate (CG) IP daily for 3 weeks, the resting group which was injected with CG IP between weeks 0-3 followed by a peritoneal rest period between weeks 3-6, and the CG + Imatinib mesylate group (CG + IMA) which received CG through weeks 0-3 followed by 50 mg/kg imatinib mesylate through weeks 3-6. At the end of the study, we performed a 1-h-peritoneal equilibration test and examined the peritoneal function and transforming growth factor-β1 (TGF-β1) in dialysate. Morphologic changes were evaluated by microscopy and immunohistochemistry.
  
  
  RESULTS
  An increased ultrafiltration, dialysate/plasma-creatinine-ratio, end-to-initial-dialysate-glucose-ratio, decreased active mesothelial cell ratio and inflammation, and a slightly decreased TGF-β1 of dialysate were found in the CG + IMA group compared to CG alone. Furthermore, the CG + IMA group had a lower concentration of active mesothelial cells than did the resting group. Ultrafiltration was improved in CG + IMA group compared to resting group, however, significant decrease in peritoneal thickness and inflammation were not found compared to those in resting group. Furthermore, there was no significant difference in fibrosis or TGF-β1-positivity on immunohistochemistry between the groups.
  
  
  CONCLUSIONS
  Tyrosine kinase inhibition with imatinib may lead to a decrease in mesothelial cell activity and an increase in ultrafiltration. However, peritoneal fibrosis was unchanged by imatinib in EPS model.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Marmara University School of Medicine, Istanbul, Turkey. drarzukahveci@yahoo.com
authors.forename: Arzu
authors.initials: A
authors.lastname: Velioglu
authors.forename: Halil
authors.initials: H
authors.lastname: Tugtepe
authors.forename: Ebru
authors.initials: E
authors.lastname: Asicioglu
authors.forename: Neslihan
authors.initials: N
authors.lastname: Yilmaz
authors.forename: Deniz
authors.initials: D
authors.lastname: Filinte
authors.forename: Hakki
authors.initials: H
authors.lastname: Arikan
authors.forename: Mehmet
authors.initials: M
authors.lastname: Koc
authors.forename: Serhan
authors.initials: S
authors.lastname: Tuglular
authors.forename: Handan
authors.initials: H
authors.lastname: Kaya
authors.forename: Cetin
authors.initials: C
authors.lastname: Ozener
mesh_terms: D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D002710:Chlorhexidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004195:Disease Models, Animal; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D008297:Male; D056627:Peritoneal Fibrosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D053773:Transforming Growth Factor beta1; D000068877:Imatinib Mesylate; C010882:chlorhexidine gluconate; D002710:Chlorhexidine