The Effect of Steroid-Sirolimus Combination on the Experimental Model of Encapsulating Peritoneal Sclerosis in Rats

Abstract

A AB BS S T TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis terminating with peritoneal sclerosis and coccooning of intestinal loops. The inhibitors of mammalian target of rapamycin (mTOR), everolimus and sirolimus, have attenuated EPS findings in experimental animal models. The effect of combination of sirolimus with steroid has not been documented so far. The aim of the study was to determine the effect of combination of sirolimus and steroid on experimental sclerosing peritonitis model. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : 41 wistar albino male rats were divided into 6 groups : control group (C; isotonic saline injected intraperitoneally), chlorhexidine gluconate group (CG; model group), resting group (R; CG then peritoneal rest, prednisolone group (P; CG then prednisolone), sirolimus group (Sir; CG then sirolimus), and prednisolone-sirolimus group (P-Sir; CG then prednisolone plus sirolimus). Peritoneal specimens obtained after sacrification at the end of study were examined for peritoneal thickness, fibrosis, and vascular intensities under light microscopy. R Re es su ul lt ts s: : In the CG and R groups there was a significant increase in peritoneal thickness, fibrosis score and vascular intensity compared to C, P, Sir, and P-Sir groups in both parietal and visceral peritoneum (p<0.05). The parameters at the end of the study were not different in C, P, Sir, and P-Sir groups. The difference between P, Sir, and P-Sir groups were not significant. Resting was shown to be ineffective in attenuating EPS parameters. C Co on nc cl lu us si io on n: : In this study we observed that sirolimus-prednisolone combination was equally effective in experimental EPS model compared to prednisolone and sirolimus only regimens.K Ke ey y W Wo or rd ds s: : Peritonitis; sirolimus; models, animal; adrenal cortex hormones; peritoneal dialysis Ö ÖZ ZE ET T A Am ma aç ç: : Enkapsüle periton sklerozu (EPS), periton sklerozu ve intestinal segmentlerin koza şeklinde sarılması ile sonuçlanan ciddi bir periton diyalizi komplikasyonudur. Memelilerde rapamisin hedefi inhibitörleri (mTOR), everolimus ve sirolimus, deneysel hayvan modellerinde EPS bulgularını azaltmışlardır. Steroid-sirolimus kombinasyonunun etkisine yönelik yapılan bir çalışma bulunmamaktadır. Bu çalışmada deneysel sklerozon peritorit modelinde sirolimus ile steroid kombinasyon tedavisinin etkisini belirlemek amaçlanmıştır. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : 41 wistar albino erkek sıçan 6 gruba ayrıldı: kontrol grubu (C; intraperitoneal izotonik serum), klorheksidin glukonat grubu (CG; model grup), dinlenme grubu (R; CG sonrası periton dinlenme), prednizolon grubu (P; CG sonrası prednizolon), sirolimus grubu (Sir; CG sonrası sirolimus) ve prednizolon-sirolimus grubu (P-Sir; CG sonrası prednizolon ve sirolimus). Periton örnekleri ışık mikroskobisi ile; periton kalınlığı, fibrozis skoru ve damar yoğunluğu için değerlendirildi. B Bu ul lg gu ul l...