title: Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats.
abstract: Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1week. Rats received daily intravenous injections of calcitriol (low-dose, 10ng/kg; or high-dose, 100ng/kg) for 1week. After 7days, conventional 4.25% Dianeal (30mL) was administered via peritoneal dialysis over 4h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D4/D0 glucose) for glucose, and the dialysate-to-plasma concentration ratio (D4/P4 urea) at 4h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D4/P4 Urea level was reduced; increases were observed in the D4/D0 glucose level and the levels of active transforming growth factor-β1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-β1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-β1 and angiotensin II production.
authors.affiliation: Department of Nursing, Tzu Chi College of Technology, Hualien, Taiwan.
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Lee
authors.forename: Yi-Maun
authors.initials: YM
authors.lastname: Subeq
authors.forename: Ru-Ping
authors.initials: RP
authors.lastname: Lee
authors.forename: Hung-Hsiang
authors.initials: HH
authors.lastname: Liou
authors.forename: Bang-Gee
authors.initials: BG
authors.lastname: Hsu
mesh_terms: D000804:Angiotensin II / Q000097:blood*; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002710:Chlorhexidine / Q000031:analogs & derivatives; D015314:Dialysis Solutions / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000473:pathology; D008297:Male; D009132:Muscles / Q000166:cytology / Q000473:pathology; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D056627:Peritoneal Fibrosis / Q000188:drug therapy* / Q000517:prevention & control; D010537:Peritoneum / Q000166:cytology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D015314:Dialysis Solutions; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D002117:Calcitriol; C010882:chlorhexidine gluconate; D002710:Chlorhexidine
keywords: Angiotensin II; Calcitriol; Chlorhexidine digluconate; Peritoneal fibrosis; Transforming growth factor-β