The effect of vascular endothelial growtt factor inhibitor (bevacizumab) on sclerosing encapsulated fibrosis model in rats

Sclerosing encapsulated peritonitis (SEP) is a rare but a serious complication that may cause death occurring in peritoneal dialysis patients. Many factors may cause mesothelial cell ( MC) denution, neovascularization and peritoneal fibrosis at peritoneal membrane. Bevacizumab is a monoclonal antihuman antibody against vascular endothelial growth factor, and prevents new vessel formation and hence decreases fibrosis. It is commonly used in colorectal and breast cancers. There has been no reported study on its effects on peritoneal fibrosis.Objective : In this study it is aimed to determine the effect of Bevacizumab on peritoneal fibrosis in rat models.Materials and methods : 41 Wistar albino rats were divided into six groups : control group (K) consisted of six rats that were given isotonic serum (2 ml/day) intraperitoneally (i.p) for 21 days; chlorhexidine gluconate (CG) group (KH) (7 rats) that were given 0.1 % CG and 15 % ethyl alcohol dissolved in saline (i.p) for 21 days; rest group (D, 7 rats) and received CG (2 ml/d) for 21 days ; Bevacizumab1 (B1, 7 rats) group was given initially CG (2ml/d) for 21 days, and at day 21 Bevacizumab was applied in a dosage of 2.5 mg/kg i.p; Bevacizumab 2 ( B2, 7 rats) group received CG for 21 days and Bevacizumab two times at day 0 and 21 days of beginning of CG; Bevacizumab 3 (B3, 7 rats) group was given only Bevacizumab at day 0 and 21 in a dosage of 2.5 mg/kg. K and KH groups were sacrified at day 21, and other at day 42. Pathological specimens were taken from left anterior abdominal wall for parietal peritoneum, and from liver for visceral peritoneum. Materials were stained by Hematoxylen & Eosin (HE) and Von Gieson (VG) and examined under light microscopy for presence of peritoneal thickness, vascular proliferation, and inflammation.Results: The decrease in parietal and visceral peritoneal thicknesses were significant in both B1 and B2 groups compared to D group (p<0.05). There were no significant difference regarding parietal peritoneal inflammation in all groups. Visceral peritoneal inflammation was significantly increased in both KH and D groups compared to K group. Significant fibrosis was shown in both parietal and visceral peritoneum in KH and D groups. Attenuation of fibrosis was significant in B1 group whereas not in B2 group. Vascular scoring was increased significantly at parietal peritoneum in KH, D, abd B1 groups, and at visceral peritoneum in B2 group.Conclusion: Bevacizumab decreased histopathological peritoneal fibrosis in CG induced chemical peritonitis. We may suggest that Bevacizumab itself did not induce peritoneal fibrosis , but can prevent peritoneal fibrosis. Regarding dose and duration of therapy large-scale experimental and clinical studies are required.Key words : sclerosing encapsulated peritonitis, VEGF, bevacizumab