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Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis

Year 2015, Volume: 32 Issue: 1, 101 - 106, 01.01.2015

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

References

  • 1. Sayarlioglu H, Dogan E, Erkoc R, Ozbek H, Bayram I, Sayarlioglu M, et al. The effect of colchicine on the peritoneal membrane. Ren Fail 2006;28:69-75. [CrossRef]
  • 2. Kawaguchi Y, Kawanishi H, Mujais S, Topley N, Oreopoulos DG. Encapsulating peritoneal sclerosis: definition, etiology,diagnosis and treatment. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis. Perit Dial Int 2000;20:43-55.
  • 3. Van Westrhenen R, Aten J, Hajji N, de Boer OJ, Kunne C, de Waart DR, et al. Cyclosporin A induces peritoneal fibrosis and angiogenesis during chronic peritoneal exposure to a glucose-based, lactatebuffered dialysis solution in the rat. Blood Purif 2007;25:466-72. [CrossRef]
  • 4. Sayarlioglu H, Topal C, Sayarlioglu M, Dulger H, Dogan E, Erkoc R. Effect of glucose concentration on peritoneal inflammatory cytokines in continuous ambulatory peritoneal dialysis patients. Mediators Inflamm 2004;13:119-21. [CrossRef]
  • 5. Lin CY, Chen WP, Yang LY, Chen A, Huang TP. Persistent transforming growth factor beta 1 expression may predict peritoneal fibrosis in CAPD patients with frequent peritonitis occurrence. Am J Nephrol 1998;18:513-9. [CrossRef]
  • 6. Margetts PJ, Oh KH, Kolb M. Transforming growth factor-beta: importance in long-term peritoneal membrane changes. Perit Dial Int 2005;25:15-7.
  • 7. Douvdevani A, Rapoport J, Konforti A, Zlotnik M, Chaimovitz C. The effect of peritoneal dialysis fluid on the release of IL-1 beta and TNF alpha by macrophages/monocytes. Perit Dial Int 1993;13:112-7.
  • 8. Fealy MJ, Umansky WS, Bickel KD, Nino JJ, Morris RE, Press BH. Efficacy of rapamycin and FK 506 in prolonging rat hind limb allograft survival. Ann Surg 1994;219:88-93. [CrossRef]
  • 9. Duman S, Bozkurt D, Sipahi S, Sezak M, Ozkan S, Ertilav M, et al. Effects of everolimus as an antiproliferative agent on regression of encapsulating peritoneal sclerosis in a rat model. Adv Perit Dial 2008;24:104-10.
  • 10. Roqué M, Reis ED, Cordon-Cardo C, Taubman MB, Fallon JT, Fuster V, et al. Effect of p27 deficiency and rapamycin on intimal hyperplasia: in vivo and in vitro studies using a p27 knockout mouse model. Lab Invest 2001;81:895-903. [CrossRef]
  • 11. van Westrhenen R, Aten J, Aberra M, Dragt CA, Deira G, Krediet RT. Effects of inhibition of the polyol pathway during chronic peritoneal exposure to a dialysis solution. Perit Dial Int 2005;25 Suppl 3:18-21.
  • 12. Kalk P, Rückert M, Godes M, von Websky K, Relle K, Neumayer HH, Hocher B, Morgera S. Does endothelin B receptor deficiency ameliorate the induction of peritoneal fibrosis in experimental peritoneal dialysis? Nephrol Dial Transplant 2010;25:1474-8. [CrossRef]
  • 13. Yuan J, Fang W, Ni Z, Dai H, Lin A, Cao L, et al. Peritoneal morphologic changes in a peritoneal dialysis rat model correlate with angiopoietin/Tie-2. Pediatr Nephrol 2009;24:163-70. [CrossRef]
  • 14. Komatsu H, Uchiyama K, Tsuchida M, Isoyama N, Matsumura M, Hara T, et al. Development of a peritoneal sclerosis rat model using a continuous-infusion pump. Perit Dial Int 2008;28:641-7.
  • 15. Grassmann A, Gioberge S, Moeller S, Brown G. ESRD patients in 2004: global overview of patient numbers, treatment modalities and associated trends. Nephrol Dial Transplant 2005;20:2587-93. [CrossRef]
  • 16. Devuyst O, Margetts PJ, Topley N. The pathophysiology of the peritoneal membrane. J Am Soc Nephrol 2010;21:1077-85. [CrossRef]
  • 17. Sampimon DE, Kolesnyk I, Korte MR, Fieren MW, Struijk DG, Krediet RT. Use of angiotensin II inhibitors in patients that develop encapsulating peritoneal sclerosis. Perit Dial Int 2010;30:656-9. [CrossRef]
  • 18. Noh H, Ha H, Yu MR, Kim YO, Kim JH, Lee HB. Angiotensin II mediates high glucose-induced TGF-beta1 and fibronectin upregulation in HPMC through reactive oxygen species. Perit Dial Int 2005;25:38-47.
  • 19. Dainese L, Cappai A, Biglioli P. Recurrent pericardial effusion after cardiac surgery: the use of colchicine after recalcitrant conventional therapy. J Cardiothorac Surg 2011;10;6:96.
  • 20. Kershenobich D, Vargas F, Garcia-Tsao G, Perez Tamayo R, Gent M, Rojkind M. Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 1988;318:1709-13. [CrossRef]
  • 21. Kaplan MM, Alling DW, Zimmerman HJ, Wolfe HJ, Sepersky RA, Hirsch GS, et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986;315:1448-54. [CrossRef]
  • 22. Peters SG, McDougall JC, Douglas WW, Coles DT, DeRemee RA. Colchicine in the treatment of pulmonary fibrosis. Chest 1993;103:101-4. [CrossRef]
  • 23. Lloberas N, Cruzado JM, Franquesa M, Herrero-Fresneda I, Torras J, Alperovich G, et al. Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J Am Soc Nephrol 2006;17:1395-404. [CrossRef]
  • 24. Hartford CM, Ratain MJ. Rapamycin: something old, something new, sometimes borrowed and now renewed. Clin Pharmacol Ther 2007;82:381-8. [CrossRef]
  • 25. Korfhagen TR, Le Cras TD, Davidson CR, Schmidt SM, Ikegami M, Whitsett JA, et al. Rapamycin prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 2009;41:562-72. [CrossRef]
  • 26. Temple S, Zaltzman J, Perl J. Development of encapsulating peritoneal sclerosis in a renal transplant recipient on sirolimus immunotherapy. Perit Dial Int 2010;30:475-7. [CrossRef]
  • 27. Lloberas N, Cruzado JM, Franquesa M, Herrero-Fresneda I, Torras J, Alperovich G, et al. Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J Am Soc Nephrol 2006;17:1395-404. [CrossRef]
  • 28. Kramer S, Wang-Rosenke Y, Scholl V, Binder E, Loof T, Khadzhynov D, et al. Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1- induced chronic glomerulosclerosis of the rat. Am J Physiol Renal Physiol 2008;294:F440-9. [CrossRef]
  • 29. Peker K, Inal A, Sayar I, Sahin M, Gullu H, Inal DG, et al. Prevention of intraabdominal adhesions by local and systemic administration of immunosuppressive drugs. Iran Red Crescent Med J 2013;15:e14148. [CrossRef]
  • 30. Parsons CJ, Takashima M, Rippe RA. Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol 2007;22:79-84. [CrossRef
Year 2015, Volume: 32 Issue: 1, 101 - 106, 01.01.2015

Abstract

References

  • 1. Sayarlioglu H, Dogan E, Erkoc R, Ozbek H, Bayram I, Sayarlioglu M, et al. The effect of colchicine on the peritoneal membrane. Ren Fail 2006;28:69-75. [CrossRef]
  • 2. Kawaguchi Y, Kawanishi H, Mujais S, Topley N, Oreopoulos DG. Encapsulating peritoneal sclerosis: definition, etiology,diagnosis and treatment. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis. Perit Dial Int 2000;20:43-55.
  • 3. Van Westrhenen R, Aten J, Hajji N, de Boer OJ, Kunne C, de Waart DR, et al. Cyclosporin A induces peritoneal fibrosis and angiogenesis during chronic peritoneal exposure to a glucose-based, lactatebuffered dialysis solution in the rat. Blood Purif 2007;25:466-72. [CrossRef]
  • 4. Sayarlioglu H, Topal C, Sayarlioglu M, Dulger H, Dogan E, Erkoc R. Effect of glucose concentration on peritoneal inflammatory cytokines in continuous ambulatory peritoneal dialysis patients. Mediators Inflamm 2004;13:119-21. [CrossRef]
  • 5. Lin CY, Chen WP, Yang LY, Chen A, Huang TP. Persistent transforming growth factor beta 1 expression may predict peritoneal fibrosis in CAPD patients with frequent peritonitis occurrence. Am J Nephrol 1998;18:513-9. [CrossRef]
  • 6. Margetts PJ, Oh KH, Kolb M. Transforming growth factor-beta: importance in long-term peritoneal membrane changes. Perit Dial Int 2005;25:15-7.
  • 7. Douvdevani A, Rapoport J, Konforti A, Zlotnik M, Chaimovitz C. The effect of peritoneal dialysis fluid on the release of IL-1 beta and TNF alpha by macrophages/monocytes. Perit Dial Int 1993;13:112-7.
  • 8. Fealy MJ, Umansky WS, Bickel KD, Nino JJ, Morris RE, Press BH. Efficacy of rapamycin and FK 506 in prolonging rat hind limb allograft survival. Ann Surg 1994;219:88-93. [CrossRef]
  • 9. Duman S, Bozkurt D, Sipahi S, Sezak M, Ozkan S, Ertilav M, et al. Effects of everolimus as an antiproliferative agent on regression of encapsulating peritoneal sclerosis in a rat model. Adv Perit Dial 2008;24:104-10.
  • 10. Roqué M, Reis ED, Cordon-Cardo C, Taubman MB, Fallon JT, Fuster V, et al. Effect of p27 deficiency and rapamycin on intimal hyperplasia: in vivo and in vitro studies using a p27 knockout mouse model. Lab Invest 2001;81:895-903. [CrossRef]
  • 11. van Westrhenen R, Aten J, Aberra M, Dragt CA, Deira G, Krediet RT. Effects of inhibition of the polyol pathway during chronic peritoneal exposure to a dialysis solution. Perit Dial Int 2005;25 Suppl 3:18-21.
  • 12. Kalk P, Rückert M, Godes M, von Websky K, Relle K, Neumayer HH, Hocher B, Morgera S. Does endothelin B receptor deficiency ameliorate the induction of peritoneal fibrosis in experimental peritoneal dialysis? Nephrol Dial Transplant 2010;25:1474-8. [CrossRef]
  • 13. Yuan J, Fang W, Ni Z, Dai H, Lin A, Cao L, et al. Peritoneal morphologic changes in a peritoneal dialysis rat model correlate with angiopoietin/Tie-2. Pediatr Nephrol 2009;24:163-70. [CrossRef]
  • 14. Komatsu H, Uchiyama K, Tsuchida M, Isoyama N, Matsumura M, Hara T, et al. Development of a peritoneal sclerosis rat model using a continuous-infusion pump. Perit Dial Int 2008;28:641-7.
  • 15. Grassmann A, Gioberge S, Moeller S, Brown G. ESRD patients in 2004: global overview of patient numbers, treatment modalities and associated trends. Nephrol Dial Transplant 2005;20:2587-93. [CrossRef]
  • 16. Devuyst O, Margetts PJ, Topley N. The pathophysiology of the peritoneal membrane. J Am Soc Nephrol 2010;21:1077-85. [CrossRef]
  • 17. Sampimon DE, Kolesnyk I, Korte MR, Fieren MW, Struijk DG, Krediet RT. Use of angiotensin II inhibitors in patients that develop encapsulating peritoneal sclerosis. Perit Dial Int 2010;30:656-9. [CrossRef]
  • 18. Noh H, Ha H, Yu MR, Kim YO, Kim JH, Lee HB. Angiotensin II mediates high glucose-induced TGF-beta1 and fibronectin upregulation in HPMC through reactive oxygen species. Perit Dial Int 2005;25:38-47.
  • 19. Dainese L, Cappai A, Biglioli P. Recurrent pericardial effusion after cardiac surgery: the use of colchicine after recalcitrant conventional therapy. J Cardiothorac Surg 2011;10;6:96.
  • 20. Kershenobich D, Vargas F, Garcia-Tsao G, Perez Tamayo R, Gent M, Rojkind M. Colchicine in the treatment of cirrhosis of the liver. N Engl J Med 1988;318:1709-13. [CrossRef]
  • 21. Kaplan MM, Alling DW, Zimmerman HJ, Wolfe HJ, Sepersky RA, Hirsch GS, et al. A prospective trial of colchicine for primary biliary cirrhosis. N Engl J Med 1986;315:1448-54. [CrossRef]
  • 22. Peters SG, McDougall JC, Douglas WW, Coles DT, DeRemee RA. Colchicine in the treatment of pulmonary fibrosis. Chest 1993;103:101-4. [CrossRef]
  • 23. Lloberas N, Cruzado JM, Franquesa M, Herrero-Fresneda I, Torras J, Alperovich G, et al. Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J Am Soc Nephrol 2006;17:1395-404. [CrossRef]
  • 24. Hartford CM, Ratain MJ. Rapamycin: something old, something new, sometimes borrowed and now renewed. Clin Pharmacol Ther 2007;82:381-8. [CrossRef]
  • 25. Korfhagen TR, Le Cras TD, Davidson CR, Schmidt SM, Ikegami M, Whitsett JA, et al. Rapamycin prevents transforming growth factor-alpha-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 2009;41:562-72. [CrossRef]
  • 26. Temple S, Zaltzman J, Perl J. Development of encapsulating peritoneal sclerosis in a renal transplant recipient on sirolimus immunotherapy. Perit Dial Int 2010;30:475-7. [CrossRef]
  • 27. Lloberas N, Cruzado JM, Franquesa M, Herrero-Fresneda I, Torras J, Alperovich G, et al. Mammalian target of rapamycin pathway blockade slows progression of diabetic kidney disease in rats. J Am Soc Nephrol 2006;17:1395-404. [CrossRef]
  • 28. Kramer S, Wang-Rosenke Y, Scholl V, Binder E, Loof T, Khadzhynov D, et al. Low-dose mTOR inhibition by rapamycin attenuates progression in anti-thy1- induced chronic glomerulosclerosis of the rat. Am J Physiol Renal Physiol 2008;294:F440-9. [CrossRef]
  • 29. Peker K, Inal A, Sayar I, Sahin M, Gullu H, Inal DG, et al. Prevention of intraabdominal adhesions by local and systemic administration of immunosuppressive drugs. Iran Red Crescent Med J 2013;15:e14148. [CrossRef]
  • 30. Parsons CJ, Takashima M, Rippe RA. Molecular mechanisms of hepatic fibrogenesis. J Gastroenterol Hepatol 2007;22:79-84. [CrossRef
There are 30 citations in total.

Details

Other ID JA96BU44ZS
Journal Section Research Article
Authors

Tamer Sağıroğlu This is me

Serhat Oğuz This is me

Mustafa Burak Sayhan This is me

Mehmet A. Yağcı This is me

Tülin Yalta This is me

Gönül Sağıroğlu This is me

Elif Çopuroğlu This is me

Publication Date January 1, 2015
Published in Issue Year 2015 Volume: 32 Issue: 1

Cite

APA Sağıroğlu, T., Oğuz, S., Sayhan, M. B., Yağcı, M. A., et al. (2015). Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis. Balkan Medical Journal, 32(1), 101-106.
AMA Sağıroğlu T, Oğuz S, Sayhan MB, Yağcı MA, Yalta T, Sağıroğlu G, Çopuroğlu E. Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis. Balkan Medical Journal. January 2015;32(1):101-106.
Chicago Sağıroğlu, Tamer, Serhat Oğuz, Mustafa Burak Sayhan, Mehmet A. Yağcı, Tülin Yalta, Gönül Sağıroğlu, and Elif Çopuroğlu. “Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis”. Balkan Medical Journal 32, no. 1 (January 2015): 101-6.
EndNote Sağıroğlu T, Oğuz S, Sayhan MB, Yağcı MA, Yalta T, Sağıroğlu G, Çopuroğlu E (January 1, 2015) Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis. Balkan Medical Journal 32 1 101–106.
IEEE T. Sağıroğlu, S. Oğuz, M. B. Sayhan, M. A. Yağcı, T. Yalta, G. Sağıroğlu, and E. Çopuroğlu, “Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis”, Balkan Medical Journal, vol. 32, no. 1, pp. 101–106, 2015.
ISNAD Sağıroğlu, Tamer et al. “Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis”. Balkan Medical Journal 32/1 (January 2015), 101-106.
JAMA Sağıroğlu T, Oğuz S, Sayhan MB, Yağcı MA, Yalta T, Sağıroğlu G, Çopuroğlu E. Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis. Balkan Medical Journal. 2015;32:101–106.
MLA Sağıroğlu, Tamer et al. “Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis”. Balkan Medical Journal, vol. 32, no. 1, 2015, pp. 101-6.
Vancouver Sağıroğlu T, Oğuz S, Sayhan MB, Yağcı MA, Yalta T, Sağıroğlu G, Çopuroğlu E. Comparison of Sirolimus and Colchicine Treatment on the Development of Peritoneal Fibrozis in Rats Having Peritoneal Dialysis. Balkan Medical Journal. 2015;32(1):101-6.