Effects of ursodeoxycholic acid on hemodynamic and renal function abnormalities induced by obstructive jaundice in rats.
The mechanism of renal function abnormalities in experimental biliary cirrhosis can be partially explained by the absence of gastrointestinal bile flow, which predisposes to translocation of intestinal endotoxin, a potent renal vasoconstrictor. Since bile acids prevent the absorption of intestinal endotoxins, we aimed to evaluate the effects of ursodeoxycholic acid (UDCA) administration on renal function and hemodynamic abnormalities induced by 1 week of obstructive jaundice in rats.


METHODS
Fifty-two rats were used; 30 had ligation of the common bile duct, 22 were sham operated. Bile duct ligated rats were randomly and blindly assigned to receive UDCA (25 mg/kg/day, n = 14) or placebo (n = 16) during 1 week. Sham rats received no treatment. Portal pressure (PP) as well as creatinine clearance (CrCl), urinary sodium (US), and plasma renin activity (PRA) were evaluated. Results are mean +/- SEM, with a significant value of p < 0.05.


RESULTS
Portal pressure (10.4 +/- 1.1 vs. 12.1 +/- 0.8 mm Hg) was significantly lower in UDCA than in placebo-treated rats. ALT serum levels were also significantly lower in bile duct ligated rats receiving UDCA (77.3 +/- 28 IU/L) than in placebo-treated rats (162 +/- 65 IU/L). US (1.1 +/- 0.5 vs. 2.1 +/- 0.3 mEq/24 h) was significantly lower and PRA (6.0 +/- 2.6 vs. 1.9 +/- 1.0 ng Ang 1/mL/h) higher in bile duct ligated than in sham-operated rats. No differences were found between UDCA or placebo-treated bile duct ligated rats. CrCl was similar between sham (0.39 +/- 0.12 mL/min/100 g BW) and UDCA (0.32 +/- 0.16) but significantly lower in placebo-treated (0.28 +/- 0.07) than sham-operated rats (p < 0.05).


CONCLUSIONS
UDCA administration had very mild effects on renal function abnormalities induced by experimental obstructive jaundice in rats. However, portal hypertension and biochemical abnormalities were partially improved.
Poo
J L
JL
Liver Unit, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City, Mexico.
Estanes
A
A
Pedraza-Chaverrí
J
J
Cruz
C
C
Uribe
M
M
D000704:Analysis of Variance; D000818:Animals; D002779:Cholestasis / Q000188:drug therapy* / Q000503:physiopathology; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects; D006975:Hypertension, Portal / Q000188:drug therapy / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D014580:Ursodeoxycholic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D014580:Ursodeoxycholic Acid