Impairment of maximal bilirubin secretion by cyclosporin A in the rat.
The effect of cyclosporin A on the maximal secretion of bilirubin was investigated in male Wistar rats. Following a saturating load of the pigment, intravenous administration of cyclosporin A as a single bolus (20 mg/kg) significantly reduced bile flow and bile acid secretion. The bilirubin secretory transport maximum was alos significantly reduced. The decreased excretion of the bile pigment corresponded both to bilirubin mono- and di-conjugates, the excretion of unconjugated bilirubin being slightly and non-significantly reduced. Plasma and liver bilirubin concentrations were significantly increased, while liver UDP-glucuronosyltransferase activity did not significantly differ between control and cyclosporin A-treated rats. Our data indicate that, although in cyclosporin A-treated rats there are no changes in the activities of others markers of hepatocellular dysfunction, the overall plasma to bile transfer of bilirubin is altered. The reduced hepatobiliary transport of the pigment is mainly caused by an impairment of its intracellular/canalicular transport.
Galan
A I
AI
Department of Physiology and Pharmacology, University of Salamanca, Spain.
Zapata
A J
AJ
Roman
I D
ID
Muñoz
M E
ME
Muriel
C
C
Gonzalez
J
J
Jimenez
R
R
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001663:Bilirubin / Q000097:blood / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D016572:Cyclosporine; D001663:Bilirubin