A model of chlorhexidine digluconate-induced peritoneal fibrosis in rats

Ru-Ping Lee^a, Chung-Jen Lee^b, Yi-Maun Subeq^a, Bang-Gee Hsu^{c, d}

^a Department of Nursing, Tzu Chi University, Hualien, Taiwan
^b Department of Nursing, Tzu Chi College of Technology, Hualien, Taiwan
^c School of Medicine, Tzu Chi University, Hualien, Taiwan
^d Department of Nephrology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan

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Abstract
Objectives

Peritoneal fibrosis (PF) is a recognized complication of long term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The most commonly used method to create a PF rat model is an intraperitoneal injection of 0.1% chlorhexidine gluconate with 15% ethanol. The aim of this study was to use chlorhexidine digluconate without ethanol, given via a PD catheter, to create a PF rat model.

Material and Methods

PF was induced in Sprague-Dawley rats by 0.5 mL 0.1% chlorhexidine digluconate in normal saline administered daily for 1 or 2 weeks via a PD catheter. Conventional 4.25% Dianeal dialysate solution, 30 mL, was administered via a PD catheter and the dwell time was 4 hours. Dialysate samples (0.5 mL) and blood samples (0.5 mL) were taken at 0 and 4 hours after the dialysate fluid had been infused to measure glucose and urea. At the end of dialysis, the rats were sacrificed; the parietal peritonea of the liver and anterior abdominal wall muscle were harvested. The peritoneum was analyzed by microscopic examination and immunohistochemistry for transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF).

Results

After 4 hours of PD, the D4/D0 glucose level was increased, the D4/D4 urea level was decreased, the liver and muscle peritoneum was markedly thicker, and expression of TGF-β1, α-SMA, fibronectin, collagen, and VEGF-positive cells was increased in the PF groups compared with the vehicle groups, and also in the 2 week PF group compared with the 1 week PF group.

Conclusion

We developed a novel method of creating a PF rat model using chlorhexidine digluconate without ethanol via a PD catheter, which will be useful in the study of PF.

Keywords
Chlorhexidine digluconate; Peritoneal fibrosis; Rat model