EFFECT OF INHIBITORS OF PROTEIN AND RIBONUCLEIC ACID SYNTHESIS ON THE HYPERBILIRUBINEMIA AND CHOLESTASIS PRODUCED BY -NAPHTHYLISOTHIOCYANATE

¹ Dëparlement de pharmacologie, Faculté de médecine, Université de Montréal, Montréal, Québec, Canada

The effects of actinomycin D, cycloheximide, ethionine and puromyein on the hyperbilirubinemia and cholestasis produced by -naphthylisothiocyanate (ANIT) have been studied. Pretreatment with any of the inhibitors mentioned resulted a sigiificant protection against the appearance of the elevation of plasma bilirubin concentration. In the case of actinomycin D, cycloheximide and ethionine, one-hour pretreatment was sufficient to inhibit this response to ANIT, but in the case of puromycin, it was necessary to administer multiple injections before and after ANIT to obtain a similar effect. A time-response study showed that cycloheximide and ethionine prevented completely the appearance of ANIT-induced hyperbilirubinemia even when administered 24 hours before ANIT. Actinomycin D offered only a partial protection and this only occurred up to 12 hours pretreatment. Post-treatment with actinomycin D, cycloheximide or ethionine also resulted an inhibition of the hyperbilirubinemic response. The inhibitory effect of actinomycin D, cycloheximide and ethionine was only temporary ; 48 hours after the administration of ANIT, hyperbilirubinemia was present in inhihitor-pre-treated animals as well as in those who had received only ANIT. The results suggest that unimparied protein synthesis may be involved in some of the hepatotoxic effects of ANIT.