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A novel angiogenesis inhibitor, sunitinib malate, in encapsulating peritoneal sclerosis
Devrim Bozkurt1, Banu Sarsik, Ender Hur
1Department of Nephrology, Ege University, Bornova, Izmir - Turkey. devrim_bozkurt@yahoo.com
Introduction:
Encapsulated peritoneal sclerosis (EPS) is characterized by neoangiogenesis and fibrosis. Increased inflammation is the leading cause of EPS. In turn, neoangiogenesis is both a consequence of and contributor to inflammation. The effects of sunitinib, a multitargeted receptor tyrosine kinase inhibitor, have been postulated in various antiangiogenesis, antiinflammatory and antifibrotic processes both in vitro and in vivo. This novel angiogenesis inhibitor, Sutent (sunitinib malate), was investigated in our rat EPS model.
Materials And Methods:
Forty nonuremic Wistar albino rats were divided into 4 groups as follows: 2-mL isotonic saline intraperitoneally (i.p.) daily, for 3 weeks (control group); daily 2 ml/200 g injection i.p. of chlorhexidine gluconate (0.1%) and ethanol (15%) dissolved in saline, 3 weeks (CG group); CG + additional 3 weeks without any treatment, total 6 weeks (resting group); and CG + additional 3 weeks 1 mg/kg daily Sutent (SUT) in drinking water, total 6 weeks (SUT group). At the end of the study, 1-hour PET was performed. Functional parameters and morphological changes of peritoneum with dialysate cytokine levels were examined.
Results:
SUT renewed ultrafiltration failure, D1/D0 glucose levels and dialysate protein loss. Peritoneal thickness, white blood cell count and inflammation of peritoneum were also decreased with SUT treatment. SUT significantly improved overexpression of dialysate transforming growth factor-ß1, monocyte chemoattractant protein-1 and vascular endothelial growth factor (VEGF) levels as compared with resting group.
Conclusion:
In conclusion, SUT might preserve membrane viability even at lower dosages. Although this is an experimental study, we believe that SUT after controlled trials may be a therapeutic agent for long-term peritoneal dialysis patients.
Insights
Sunitinib (SUT) improved peritoneal membrane function and reduced inflammation in a rat model of encapsulated peritoneal sclerosis (EPS). This angiogenesis inhibitor shows promise for treating long-term peritoneal dialysis patients.
Area of Science:
- Nephrology
- Oncology
- Biomedical Engineering
Background:
- Encapsulated peritoneal sclerosis (EPS) is characterized by inflammation, neoangiogenesis, and fibrosis.
- Sunitinib (SUT) is a multitargeted receptor tyrosine kinase inhibitor with potential antiangiogenic, anti-inflammatory, and antifibrotic effects.
Purpose of the Study:
- To investigate the efficacy of sunitinib (SUT) in a rat model of encapsulated peritoneal sclerosis (EPS).
Main Methods:
- Rats with EPS were treated with sunitinib (SUT) or saline.
- Peritoneal functional parameters, morphological changes, and dialysate cytokine levels were assessed.
Main Results:
- Sunitinib (SUT) treatment reversed ultrafiltration failure and reduced protein loss.
- SUT decreased peritoneal thickness, inflammation, and key pro-angiogenic/pro-inflammatory factors like VEGF.
Conclusions:
- Sunitinib (SUT) may preserve peritoneal membrane viability in EPS.
- SUT shows potential as a therapeutic agent for long-term peritoneal dialysis patients.
