Efflux of Bilirubin into Plasma following Hepatic Degradation of Exogenous Heme 1 2

Summary

In rats, unconjugated [³H]BR appeared in plasma within 10 min and reached a maximum concentration 60-90 min after intravenous administration of trace amounts of [³H]heme. Total hepatectomy virtually abolished plasma heme disappearance and markedly reduced the early plasma appearance of [³H]BR, thereby confirming the central role of the liver in plasma heme disposal and the hepatic origin of BR derived from it. In heterozygous Gunn rats, which have reduced BR UDP glucuronyltransferase activity, results were similar to those in normal rats. This indicates that the efflux of BR from liver to plasma did not result from BR production exceeding the hepatic BR conjugating capacity. After simultaneous injection of trace amounts of [¹⁴C]ALA (to label endog-enously synthesized hepatic heme) and [³H]heme, both [¹⁴C]- and [³H]BR appeared in plasma with strikingly similar temporal profiles. The results of these studies show directly that a considerable proportion of BR derived from hepatic heme passes to the plasma before its ultimate biliary excretion. Moreover, the kinetic profile reflecting hepatic BR production from administered heme conforms closely to the established pattern for that of early-labeled BR. These findings offer further experimental support for the concept that injected heme is incorporated into a labile unassigned heme pool in the liver.

We are grateful to Ms. Nancy Wang for typing the manuscript and to Ms. Diana Fedorchak for editorial assistance.