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Effect of sirolimus on the regression of peritoneal sclerosis in an experimental rat model

Abstract

Purpose

Immunosuppressive and anti-inflammatory agents have recently become increasingly popular in the treatment of encapsulating peritoneal sclerosis (EPS). The aim of our study was to investigate the effects of sirolimus on EPS in a rat model.

Methods

We separated 32 non-uremic rats into four groups: 1 control group, 2 ml isotonic saline injected IP daily for 3 weeks; 2 chlorhexidine gluconate (CG) group, 2 ml 0,1 % CG and 15 % ethanol dissolved in saline injected IP daily for 3 weeks; 3 resting group, CG (weeks 0–3) plus peritoneal rest (weeks 3–6); 4 sirolimus group, CG (weeks 0–3), plus 0.2 ml (1 mg/ml) sirolimus (weeks 3–6). Pathological samples were examined by using hematoxylin eosin (HE) and Masson’s trichrome stains. Peritoneal thickness, fibrosis, vascular changes, and inflammation were evaluated by light microscopy. Finally, tissue metalloproteinase (MMP)-2 levels were measured by enzyme-linked immunoassay.

Results

In the CG group, there was a significant increase in peritoneal thickness, inflammatory activity, and fibrosis score compared to the control group (p < 0.05). We also observed a lower fibrosis score and less peritoneal thickening in the sirolimus group compared to the resting and CG groups (p < 0.05). There was no difference in histopathologic findings, except for the inflammatory activity in the sirolimus group, compared to the control group. Although the CG group had higher tissue MMP-2 levels than the control group, the tissue MMP-2 levels were not significantly different from the other groups.

Conclusions

Sirolimus has a beneficial effect on peritoneal fibrosis induced by CG. This suggests that sirolimus may have therapeutic value in the management of EPS.

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Fig. 1

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Correspondence to Mevlut Ceri.

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Ceri, M., Unverdi, S., Dogan, M. et al. Effect of sirolimus on the regression of peritoneal sclerosis in an experimental rat model. Int Urol Nephrol 44, 977–982 (2012). https://doi.org/10.1007/s11255-012-0167-3

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Keywords

  • Chlorhexidine gluconate
  • Fibrosis
  • Peritoneal dialysis
  • Sirolimus