Search

Treatment of mice with phenobarbital significantly enhanced the disappearance of exogenously administered bilirubin from the plasma. Not only did this enhanced disappearance occur in the absence of biliary excretion but it was accompanied by liver bilirubin concentrations exceeding those found in controls. Both observations suggest enhanced uptake of free bilirubin by the liver as one cause of the faster rate of disappearance of bilirubin from plasma. In rats, the maximal rate of bilirubin excretion was enhanced by treatment with phenobarbital. The bile volume was also greater in phenobarbital-treated animals than in controls. The concentration of bilirubin in the bile was not significantly different, indicating that the increase in bilirubin excretion was probably due to the increase in bile volume. Indirectly, some of the data suggest that increased bilirubin conjugation may play a role in the enhanced uptake and excretion of bilirubin after phenobarbital treatment.

In an attempt to explain the inhibition of α-naphthylisothiocyanate (ANIT)induced hyperbilirubinemia by inhibitors of protein and RNA synthesis, the effect of cycloheximide, ethionine and actinomycin D on the increased bilirubin formation produced by ANIT was studied. Cycloheximide and ethionine pretreatment inhibited the ANIT-induced increase in biliary bilirubin excretion and incorporation of δ-aminolevulinic acid- 14 C (ALA- 14 C) into bilirubin. Cycloheximide was found to be more effective than ethionine in diminishing the stimulation of bilirubin production by ANIT. Pretreatment with actinomycin D prevented the ANIT-induced increase in biliary bilirubin excretion and produced a decreased, but irregular incorporation of ALA- 14 C into bilirubin. β-Naphthylisothiocyanate, which does not produce hyperbilirubinemia, failed to enhance biliary bilirubin excretion. The results suggest that the enhancement of bilirubin formation by ANIT plays a role in the overall hyperbilirubinemic response seen after ANIT administration. The inhibition of the enhanced bilirubin formation by Cycloheximide and ethionine may partially account for their inhibition of ANIT hyperbilirubinemia.