Role of rosiglitazone in lipopolysaccharide-induced peritonitis: a rat peritoneal dialysis model.
OBJECTIVE
The aim of this study was to demonstrate the efficacy of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist, rosiglitazone, in the amelioration or prevention of inflammation including peritoneal fibrosis secondary to the peritonitis in a peritoneal dialysis (PD) model of non-uraemic rats.


METHODS
Thirty male Sprague-Dawley rats were assigned to six groups according to treatment. A 90 min peritoneal equilibrium test, dialysate cellular components, peritoneal thickness and cellularity were assessed on day 21. Additionally, immunohistochemical stains of peritoneal membrane, such as PPAR-gamma, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta1, collagen-1 and monocyte chemoattractant protein-1 were performed.


RESULTS
The dialysate neutrophil count and peritoneal thickness in the high-dose rosiglitazone group was significantly decreased compared to the lipopolysaccharide (LPS)-only group. The peritoneal membrane from the LPS-only group showed marked cellular proliferation in the area of the submesothelial compact zone compared with the PD-only group, the rosiglitazone-only group, and the high-dose rosiglitazone group. The 90 min peritoneal equilibrium test (PET) results showed no statistical difference among the six groups excluding dialysate-to-plasma urea ratio. The number of PPAR-gamma expressing cells and the expression of TGF-beta1 were decreased in the high-dose rosiglitazone group compared to the LPS-only group. There were no differences in the expression of VEGF and collagen-1 among the six groups. Interestingly, the number of PPAR-gamma-positive cells was correlated with expression of VEGF, TGF-beta1, collagen-1 and monocyte chemoattractant protein-1 irrespective of the study group.


CONCLUSIONS
The results of this study showed that rosiglitazone ameliorated peritoneal inflammation induced by LPS and reduced the TGF-beta1 expression in the peritoneal membranes.
Song
Sang Heon
SH
Department of Internal Medicine, Pusan National University Hospital, Ami-dong, Seo-gu, Busan, Korea. shsong@pusan.ac.kr
Kwak
Ihm Soo
IS
Yang
Byeong Yun
BY
Lee
Dong Won
DW
Lee
Soo Bong
SB
Lee
Min Young
MY
D000818:Animals; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D023421:Models, Animal; D047495:PPAR gamma / Q000819:agonists* / Q000032:analysis; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000473:pathology; D010538:Peritonitis / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D008070:Lipopolysaccharides; D047495:PPAR gamma; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D000077154:Rosiglitazone