Effect of bevacizumab, a vascular endothelial growth factor inhibitor, on a rat model of peritoneal sclerosis

Abstract

Purpose: Peritoneal fibrosis is almost uniform feature encountered in peritoneal dialysis patients. The transition of epithelial cells to mesenchymal phenotype, neovascularization, and consequently development of peritoneal fibrosis occur due to the involvement of peritoneal membrane by various insults such as uremia itself, peritonitis attacks, and exposure to bio-incompatible peritoneal dialysis fluids. Bevacizumab is a monoclonal antihuman antibody developed against vascular endothelial growth factor and can reduce fibrosis by preventing neovascularization. There has been no study so far that demonstrates the effect of bevacizumab on peritoneal fibrosis in a rat model.

Methods: A total of 41 female Wistar albino rats were divided into six groups. The control group (C) received 0.9 % isotonic saline (2 ml/day) intraperitoneally (i.p) for 21 days. Chlorhexidine group (CH) received 15 % ethyl alcohol and 0.1 % chlorhexidine gluconate (CG) in saline (2 ml/day) i.p for 21 days. The resting group (R) received CG 2 ml/day i.p for 21 days. The bevacizumab-1 group (B1) received CG 2 ml/day i.p for 21 days and bevacizumab 2.5 mg/kg i.p as a single dose on day 21. The bevacizumab-2 group (B2) received CG 2 ml/day for 21 days and bevacizumab 2.5 mg/kg i.p on day 0 and day 21. The bevacizumab-3 group (B3) received bevacizumab 2.5 mg/kg i.p on day 0 and day 21. Peritoneal samples were taken from the left anterior abdominal wall. The thickness, vascularization, and fibrosis scores in the peritoneal samples were assessed using a light microscope.

Results: On histopathological evaluations, peritoneum thicknesses, vascularization scores, and fibrosis significantly decreased in bevacizumab groups B1 and B2.

Conclusion: Histopathologically, bevacizumab was proven to attenuate fibrotic process in experimental peritoneal sclerosis model.

Keywords: Fibrosis; Growth factors; Peritoneal dialysis; Peritoneal membrane.