evaluation of anti fibrotic role of inhibitors of 5 ht 3 isobutyl 1 methylxanthine and 5 ht2b sb204741 on fibroblasts isolated from peritoneum of patients on continuous ambulatory peritoneal dialysis

Abstract

Peritoneal fibrosis (PF) results in ultrafiltration failure in continuous ambulatory peritoneal dialysis (CAPD) patients. Despite of the advantages of being much more simple and cheaper than hemodialysis, one of the most important issues in CAPD is the long-term preservation of the peritoneum function and subsequently delaying of PF. PF is associated with UF failure, which leads to stoppage of the CAPD by the patients and UF capacity across the peritoneum is a major predictor of outcome and mortality in CAPD patients. The healthy peritoneum consists of a single-cell layer of mesothelial cells known as peritoneal mesothelial cells (PMCs) that sit over the basement membrane and maintain a smooth surface that prevents adhesion within the peritoneal cavity. Pathological changes in the peritoneal membrane during long term PD represent reduction or loss of mesothelial cells and enlargement, thickening and hyalinizing vasculopathy of the sub-mesothelial compact zone because of interstitial fibrosis, accompanied by neo-angiogenesis and also the inflammation promoted by the non-physiological content of solutions and infections. The most important feature that was noted was the universal absence of a mesothelial layer in the perspective of thickening of sub-mesothelial layer, representing tissue fibrosis. In addition to its clinical importance for CAPD patients, the peritoneum provides a unique and simple organ structure for fibrosis research. The most important agents responsible for PF include components of dialysis solution, mainly glucose, glucose degradation products (GDPs) and advanced glycation end products (AGEs). Long term continuous exposure to non-physiological dialysis solution results in a reduction in ultrafiltration (UF), loss of the mesothelial cell layer and sub-mesothelial layer thickening that constitute increased myo-fibroblasts (MFBs), collagen deposition and sub-mesothelial fibrosis. newline