Effect of bevacizumab and everolimus combination treatment on peritoneal sclerosis in an experimental rat model

Abstract

The aim of this study was to investigate whether bevacizumab and everolimus combination therapy is superior to bevacizumab treatment alone as a treatment for peritoneal sclerosis. Forty Wistar albino rats were divided into five equal groups. The control group received isotonic saline solution (2 mL/day) intraperitoneal (IP) daily for 3 weeks. The CG group received 2 mL 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline IP daily for 3 weeks. Peritoneal tissue samples were taken at the end of 3 weeks. The resting group received CG (weeks 0-3), plus isotonic saline solution (2 mL/day) IP daily and tap water (2 mL/day) via a feeding tube daily (weeks 3-6).The bevacizumab group received CG (weeks 1-3) plus bevacizumab at 2.5 mg/kg/day (2 mL) IP daily and tap water (2 mL/day) via a feeding tube daily (weeks 3-6). The bevacizumab+everolimus group received CG (weeks 1-3) plus bevacizumab at 2.5 mg/kg/day (2 mL) IP daily and everolimus at 0.3 mg/kg/day (2 mL) via a feeding tube daily (weeks 3-6). Peritoneal tissue samples were taken from these three groups at the end of 6 weeks and were examined after staining with hematoxylin-eosin and Masson's trichrome. Inflammation, vasculopathy, fibrosis, and peritoneal thickness were evaluated under light microscopy. The samples were also stained with anti-TGF-ß and anti-MMP-2. Inflammation and vasculopathy scores were significantly decreased in the VEGF-i group compared to the CG group. The addition of everolimus to VEGF-i showed significantly lower inflammation, vasculopathy, fibrosis scores, and an evident decrease in peritoneal thickening (respectively, 2.29 ± 0.76 vs 0.57 ± 0.53, P =.003; 2.71 ± 0.76 vs 1.43 ± 0.53, P =.008; 2.57 ± 0.79 vs 1.57 ± 0.79, P =.04; 247.5 ± 136.1 vs 84.5 ± 48.6, P =.048). MMP-2 levels were lower in the combination group compared to the resting group (2.63 ± 0.74 vs 1.86 ± 0.38, P =.019). The study results demonstrated that bevacizumab and everolimus combination therapy was more effective than bevacizumab therapy alone. © 2020 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy