Bilirubin excretion in rats with normal and impaired bilirubin conjugation: effect of phenobarbital

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Abstract

The effect of phenobarbital on bilirubin excretion was studied in rats with different capacities for bilirubin conjugation. Drug treatment induced substantial increases in bilirubin UDP-glucuronyl transferase activity in the liver of both normal and heterozygous Gunn rats, but not homozygous Gunn rats in which enzyme activity is completely absent. However, enhancement of bilirubin excretion in vivo was observed only in heterozygous Gunn rats. In these animals the maximum capacity to excrete bilirubin into bile (Tmax), like the activity of the conjugating enzyme, was half normal; phenobarbital caused an increase in Tmax to levels characteristic of normal animals, with a twofold rise in the excretion of conjugated pigment. This appeared to be largely unrelated to enhancement of bile flow, and there was no stimulation of alternate pathways of bilirubin excretion.

Authors

Stephen H. Robinson, Claudine Yannoni, Susumu Nagasawa