title: Prevention of lipopolysaccharide-induced peritoneal damage by eplerenone in rats undergoing peritoneal dialysis.
abstract: BACKGROUND
  Bacterial peritonitis in patients undergoing peritoneal dialysis (PD) is a major cause of therapy interruption due to peritoneal insufficiency. Here we studied the effect of a selective mineralocorticoid receptor (MR) blocker, eplerenone, on the prevention of peritoneal damage.
  
  
  METHODS
  Male Sprague-Dawley rats were treated with a daily infusion of human use PD solution (100 mL/kg i.p., PD group, n = 5), or with PD solution and intermittent intraperitoneal injections of lipopolysaccharide (LPS group, n = 5) or with LPS and eplerenone (100 mg/ kg/d, po, Ep group, n = 5) for 4 weeks. Peritoneal samples were subjected to assessment following the peritoneal equilibration test (PET).
  
  
  RESULTS
  Histological observations revealed that LPS treatment resulted in significant peritoneal thickening associated with increased ED-1-positive cell infiltration and the number of transforming growth factor (TGF)-β1-positive cells, and that eplerenone reduced these changes. LPS administration also evoked significant upregulation of monocyte chemotactic protein-1 and TGF-β1, which were inhibited by eplerenone. PET revealed that ultrafiltration and transperitoneal osmotic diffusion were significantly impaired by LPS and restored by eplerenone. Increased value of the mass transfer area coefficients for creatinine values was also recovered by Ep (0.10 ±  0.01 in the PD, 0.14 ± 0.02 in the LPS and 0.08 ± 0.0 in the Ep groups). Immunostaining for von Willebrand factor showed a significant increase by LPS and its restoration by Ep.
  
  
  CONCLUSIONS
  Ep effectively diminished LPS-induced peritoneal insufficiency. A selective blockade of MR might prevent peritoneal insufficiency associated with bacterial peritonitis.
authors.affiliation: Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Saitama - Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tayama
authors.forename: Hajime
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Takayanagi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Matsuda
authors.forename: Taisuke
authors.initials: T
authors.lastname: Shimizu
authors.forename: Juko
authors.initials: J
authors.lastname: Asakura
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Iwashita
authors.forename: Tomonari
authors.initials: T
authors.lastname: Ogawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Katoh
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitarai
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism; D003404:Creatinine; D015314:Dialysis Solutions / Q000009:adverse effects*; D000077545:Eplerenone; D008070:Lipopolysaccharides; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D009995:Osmosis / Q000187:drug effects; D010530:Peritoneal Dialysis; D010532:Peritoneal Diseases / Q000382:microbiology / Q000517:prevention & control*; D010537:Peritoneum / Q000187:drug effects / Q000473:pathology; D010538:Peritonitis / Q000188:drug therapy / Q000209:etiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014462:Ultrafiltration; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D015314:Dialysis Solutions; D008070:Lipopolysaccharides; D000451:Mineralocorticoid Receptor Antagonists; D053773:Transforming Growth Factor beta1; D014841:von Willebrand Factor; D013148:Spironolactone; D000077545:Eplerenone; D003404:Creatinine