Role of rosiglitazone in lipopolysaccharide-induced peritonitis: A rat peritoneal dialysis model

Authors


Prof. Ihm Soo Kwak, Department of Internal Me dicine and Medical Research Institute, Pusan National University Hospital, 1-10 Ami-dong, Seo-gu, Busan 602-739, Korea. Email: shsong@pusan.ac.kr

SUMMARY

Aim:  The aim of this study was to demonstrate the efficacy of the peroxisome proliferator-activated receptor (PPAR)-γ 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-γ, vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, 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-γ expressing cells and the expression of TGF-β1 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-γ-positive cells was correlated with expression of VEGF, TGF-β1, collagen-1 and monocyte chemoattractant protein-1 irrespective of the study group.

Conclusion:  The results of this study showed that rosiglitazone ameliorated peritoneal inflammation induced by LPS and reduced the TGF-β1 expression in the peritoneal membranes.

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