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.

• Authors: Mevlut Ceri, Selman Unverdi, Mehmet Dogan, Hatice Unverdi, Gokhan Karaca, Gulay Kocak, Ilhan Kurultak, Erdem Akbal, Murat Can, Murat Duranay
• Journal: International urology and nephrology (Int Urol Nephrol) Vol. 44 Issue 3 Pg. 977-82 (Jun 2012) ISSN: 1573-2584 [Electronic] Netherlands
• PMID: 22528580 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• Matrix Metalloproteinase 2
• chlorhexidine gluconate
• Chlorhexidine
• Sirolimus

Topics

• Animals
• Chlorhexidine (analogs & derivatives)
• Female
• Immunosuppressive Agents (therapeutic use)
• Matrix Metalloproteinase 2 (metabolism)
• Peritoneal Dialysis (adverse effects)
• Peritoneal Fibrosis (chemically induced, drug therapy, enzymology, pathology)
• Rats
• Rats, Wistar
• Sirolimus (therapeutic use)
• Statistics, Nonparametric