Tamer Sağıroğlu1, Mustafa Burak Sayhan2, Mehmet A Yağcı3, Tülin Yalta4, Gönül Sağıroğlu4, Elif Çopuroğlu5, Serhat Oğuz1. 1. Deptartment of General Surgery, Trakya University Faculty of Medicine, Edirne, Turkey. 2. Deparment of Emergency Medicine, Trakya University Faculty of Medicine, Edirne, Turkey. 3. Department of General Surgery, İnönü University Faculty of Medicine, Malatya, Turkey. 4. Department of Pathology, Trakya University Faculty of Medicine, Edirne, Turkey. 5. Department of Anesthesiology, Trakya University Faculty of Medicine, Edirne, Turkey.
Abstract
BACKGROUND: Continuous ambulatory peritoneal dialysis is a successful treatment modality for patients with end-stage renal disease. Peritoneal fibrosis (PF) is the most critical complication of long-term peritoneal dialysis (PD). AIMS: In our study, we aimed to compare the effects of colchicine and sirolimus on PF induced by hypertonic peritoneal dialysis solutions in rats. STUDY DESIGN: Animal experiment. METHODS: Twenty-four rats were randomly divided into three groups. The control group received an intraperitoneal injection (ip) of saline. The sirolimus group received the PD solution, plus 1.0 mg/kg/day Rapamune®. The colchicine group received the PD solution ip plus 1.0 mg/kg/day of colchicine. Blood samples were taken to measure the serum levels of VEGF, TGF-β, and TNF-α. Peritoneal tissue samples were taken for histopathological evaluation. RESULTS: TGF-β and TNF-α values in the sirolimus group were found to be statistically significantly lower than in the control and colchicine groups, but the differences between the control and colchicine groups were not statistically significant. No statistically significant differences were found between the groups regarding the VEGF values. Vascular neogenesis and peritoneal thickness were compared; the values in the sirolimus group were statistically reduced compared to the values in the control group. Mild fibrosis developed in 75% of all animals in the sirolimus group; there was no moderate or severe fibrosis observed. Fibrosis developed to varying degrees in 100% of the animals in the control and colchicine groups. CONCLUSION: The present study demonstrates that sirolimus might be beneficial for preventing or delaying the progression of PF and neoangiogenesis. These alterations in the peritoneal membrane may be connected with reduced TNF-α and TGF-β levels.
BACKGROUND: Continuous ambulatory peritoneal dialysis is a successful treatment modality for patients with end-stage renal disease. Peritoneal fibrosis (PF) is the most critical complication of long-term peritoneal dialysis (PD). AIMS: In our study, we aimed to compare the effects of colchicine and sirolimus on PF induced by hypertonic peritoneal dialysis solutions in rats. STUDY DESIGN: Animal experiment. METHODS: Twenty-four rats were randomly divided into three groups. The control group received an intraperitoneal injection (ip) of saline. The sirolimus group received the PD solution, plus 1.0 mg/kg/day Rapamune®. The colchicine group received the PD solution ip plus 1.0 mg/kg/day of colchicine. Blood samples were taken to measure the serum levels of VEGF, TGF-β, and TNF-α. Peritoneal tissue samples were taken for histopathological evaluation. RESULTS: TGF-β and TNF-α values in the sirolimus group were found to be statistically significantly lower than in the control and colchicine groups, but the differences between the control and colchicine groups were not statistically significant. No statistically significant differences were found between the groups regarding the VEGF values. Vascular neogenesis and peritoneal thickness were compared; the values in the sirolimus group were statistically reduced compared to the values in the control group. Mild fibrosis developed in 75% of all animals in the sirolimus group; there was no moderate or severe fibrosis observed. Fibrosis developed to varying degrees in 100% of the animals in the control and colchicine groups. CONCLUSION: The present study demonstrates that sirolimus might be beneficial for preventing or delaying the progression of PF and neoangiogenesis. These alterations in the peritoneal membrane may be connected with reduced TNF-α and TGF-β levels.
Authors: Roos van Westrhenen; Jan Aten; Medhanit Aberra; Cindy A M Dragt; Gregory Deira; Raymond T Krediet Journal: Perit Dial Int Date: 2005-02 Impact factor: 1.756
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