The effects of mycophenolate mofetil on encapsulated peritoneal sclerosis model in rats

Clin Nephrol. 2012 Jan;77(1):1-7. doi: 10.5414/cn107140.

Abstract

Introduction: Encapsulated peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis. We aimed to investigate the effects of mycophenolate mofetil (MMF) treatment in experimental EPS in rats.

Methods: 40 nonuremic Wistar albino rats were divided equally into 4 groups: control rats received 2 ml isotonic saline intraperitoneally daily for 3 weeks without any other treatment. The chlorhexidine gluconate group received intraperitoneally 2 ml/200 g injection of chlorhexidine gluconate and ethanol dissolved in saline for 3 weeks. The resting group received chlorhexidine gluconate (0 - 3rd week) + peritoneal resting (4th - 6th week). The MMF group received chlorhexidine gluconate (0 - 3rd week) + 125 mg/l MMF in drinking water (4th - 6th week). Dialysate cytokine levels, leukocyte count, peritoneal thickness, inflammation and fibroblast activities were evaluated.

Results: Although the MMF and resting groups showed beneficial effects on ultrafiltration and D1/D0 glucose compared to the chlorhexidine gluconate group, only MMF treatment improved dialysate TGFβ1, VEGF and MCP-1 levels compared to the resting group. Inflammatory activity and vascularity observed in a tissue biopsy, including capillaries number per mm2 of submesothelial area, decreased in the treatment group.

Conclusions: MMF treatment has beneficial effects on EPS via inhibiting inflammation and neovascularisation by reducing dialysate VEGF overexpression.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Chemokine CCL2 / metabolism
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Male
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / pharmacology
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / etiology
  • Neovascularization, Pathologic / metabolism
  • Peritoneal Dialysis / adverse effects*
  • Peritoneal Fibrosis / drug therapy*
  • Peritoneal Fibrosis / etiology*
  • Peritoneal Fibrosis / metabolism
  • Peritoneum / drug effects
  • Peritoneum / metabolism
  • Rats
  • Rats, Wistar
  • Transforming Growth Factor beta1 / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Mycophenolic Acid