Aliskiren ameliorates chlorhexidine digluconate-induced peritoneal fibrosis in rats.
BACKGROUND
Peritoneal fibrosis (PF) is a recognized complication of long-term peritoneal dialysis (PD) and can lead to ultrafiltration failure. The present study was designed to investigate the protective effects of aliskiren on chlorhexidine digluconate-induced PF in rats.


METHODS
The PF was induced in Sprague-Dawley rats by daily administration of 0.5 mL 0.1% chlorhexidine digluconate in normal saline via PD tube for 1 week. Rats received daily intravenous injections of low-dose aliskiren (1 mg kg(-1)) or high-dose aliskiren (10 mg kg(-1)) for 1 week. After 7 days, conventional 4.25% Dianeal (30 mL) was administered via a PD catheter with a dwell time of 4 h and assessed of peritoneal function. At the end of dialysis, rats were sacrificed and the liver peritoneum was harvested for microscopically and immunohistochemistry.


RESULTS
There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D(4)/P(4) urea level was reduced, the D(4)/D(0) glucose level, serum and dialysate transforming growth factor-beta1 (TGF-beta1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-beta1, alpha-smooth muscle actin (alpha-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PS group compared with the vehicle group. Aliskiren decreased the serum and dialysate TGF-beta1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-beta1, alpha-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. Moreover, high-dose aliskiren had better protective effects against PF than low dose in rats.


CONCLUSIONS
Aliskiren protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-beta1 production.
Ke
Chun-Yen
CY
Tzu Chi University, Hualien, Taiwan.
Lee
Chia-Chi
CC
Lee
Chung-Jen
CJ
Subeq
Yi-Maun
YM
Lee
Ru-Ping
RP
Hsu
Bang-Gee
BG
D000577:Amides / Q000008:administration & dosage*; D000818:Animals; D000890:Anti-Infective Agents / Q000009:adverse effects; D002710:Chlorhexidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005650:Fumarates / Q000008:administration & dosage*; D010530:Peritoneal Dialysis / Q000009:adverse effects; D056627:Peritoneal Fibrosis / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D016896:Treatment Outcome
D000577:Amides; D000890:Anti-Infective Agents; D005650:Fumarates; D053773:Transforming Growth Factor beta1; C446481:aliskiren; D012083:Renin; C010882:chlorhexidine gluconate; D002710:Chlorhexidine