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Analysis of thalidomide and the infusion of mesenchymal stem cells derived from adipose tissue in an experimental model of peritoneal fibrosis in rats with chronic kidney disease

Grant number: 12/13949-6
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2012
Effective date (End): July 31, 2014
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Irene de Lourdes Noronha
Grantee:Amanda Gonçalves Pires
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Peritoneal dialysis is an important therapeutic option for patients with chronic kidney disease (CKD) in the terminal stage. However, during the treatment, this therapy presents the development of peritoneal inflammation and fibrosis due to several factors, including the incompatibility of solutions, with its high concentration of glucose the main determinant of the activation of the inflammatory response. Strategies to prevent peritoneal inflammation and fibrosis and restore the peritoneal tissue are extremely important for dialysis patients. In this context, this study aims to analyze the effect of thalidomide, an immunomodulatory drug, and mesenchymal stem cells in an experimental model of peritoneal fibrosis in rats with chronic kidney disease (CKD) with uremia. The CKD with uremia will be induce in male Wistar rats by administration of adenine rich diet in the concentration of 0,75% during 30 days. On day 15 the animals will receive intraperitoneal injections of chlorhexidine gluconate for the induction of peritonitis and accordingly will be treated with thalidomide or mesenchymal stem cells . During the 30 day of follow-up, the weight, blood pressure, serum urea and creatinine will be analyzed. At the end of the study, animals will be sacrificed. To evaluate the thickness and peritoneal fibrosis, the histological technique of Masson thricome will be used. In addition, there will be immunohistochemistry for macrophages, T lymphocytes and myofibroblasts. And real-time PCR to analyze gene expression of MCP-1, VEGF, TGF-ß, IL-1ß, TNF-±, IL-6, collagen I and III. The present study will demonstrate the effects of thalidomide and mesenchymal stem cells in an experimental model of peritoneal fibrosis developed in uremic rats with CKD.