Valsartan decreases TGF-β1 production and protects against chlorhexidine digluconate-induced liver peritoneal fibrosis in rats.
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 valsartan on chlorhexidine digluconate-induced PF by decreasing TGF-β1 production in rats. PF was induced in Sprague-Dawley rats by daily administration of 0.5 ml 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis (PD) tube for 1 week. Rats received daily intravenous injections of low dose valsartan (1 mg/kg) or high dose valsartan (3 mg/kg) 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. There was no significant difference in mean arterial pressure and heart rate between groups. After 4 h of PD, the D₄/P(4Urea) level was reduced, the D₄/D₀ glucose level, serum and dialysate transforming growth factor-β1 (TGF-β1) level was increased, the liver peritoneum was markedly thicker, and the expression of TGF-β1, alpha-smooth muscle actin (α-SMA), fibronectin, collagen, and vascular endothelial growth factor (VEGF) were elevated in the PF group compared with the vehicle group. High dose of valsartan decreased the serum and dialysate TGF-β1 level, decreased the thickness of the liver peritoneum, and decreased the expression of TGF-β1, α-SMA, fibronectin, collagen, and VEGF-positive cells in liver peritoneum. The low dose of valsartan did not protect against chlorhexidine digluconate-induced PF in rat. Valsartan protected against chlorhexidine digluconate-induced PF in rats by decreasing TGF-β1 production.
Department of Nursing, Tzu Chi University, Hualien, Taiwan.
Yi-Maun
YM
Subeq
Chen-Yen
CY
Ke
Nien-Tsung
NT
Lin
Chung-Jen
CJ
Lee
Yi-Han
YH
Chiu
Bang-Gee
BG
Hsu
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002710:Chlorhexidine / Q000031:analogs & derivatives; D005947:Glucose / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D010530:Peritoneal Dialysis; D056627:Peritoneal Fibrosis / Q000097:blood / Q000150:complications* / Q000503:physiopathology / Q000517:prevention & control*; D010537:Peritoneum / Q000473:pathology / Q000503:physiopathology; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013194:Staining and Labeling; D013777:Tetrazoles / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000097:blood; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D020011:Protective Agents; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D000068756:Valsartan; D014633:Valine; D005947:Glucose; C010882:chlorhexidine gluconate; D002710:Chlorhexidine