BILE-ACID CLEARANCE IN SHEEP WITH HEREDITARY HYPER-BILITRUBINEMIA

  • 1 January 1979
    • journal article
    • research article
    • Vol. 40  (9) , 1277-1280
Abstract
The disappearance of i.v. injected [24-14C]cholic acid from plasma was studied in normal and mutant Corriedale and Southdown sheep exhibiting hereditary defects in hepatic organic anion transport. Hepatic cholic acid clearance was determined from the integral of the 40-min disappearance curves fit to the sums of 2 exponential functions. Cholic acid clearance among Corriedale sheep was significantly less (P < 0.05) for mutant sheep (8.44 .+-. 0.86 SE ml/min. per kg of body weight) than for normal sheep (12.7 .+-. 0.58 ml/minute per kg). Cholic acid clearance in the Southdown mutant (1.97 .+-. 0.59 ml/minute per kg) was < 15% of normal clearance rate (13.3 .+-. 2.2 ml/minute per kg). Clearance of [14C]taurocholic acid (curves fit to 3 exponential function) in the Southdown mutant (10.8 .+-. 0.4 ml/minute per kg) was significantly greater (P < 0.01) than cholic acid clearance, yet was not significantly different (P > 0.05) from normal taurocholate clearance (17.8 .+-. 2.5 ml/minute per kg). Hepatic regurgitation of conjugated bile acid was not detected after [14C]cholic acid injection. Both the mutant Corriedale and Southdown sheep, which exhibited inherited defects in hepatic bilirubin transport similar to Dubin-Johnson syndrome and Gilbert''s disease in man, exhibited defects in hepatic bile acid clearance.