EFFECTS OF INHIBITORS OF PROTEIN AND RIBONUCLEIC ACID SYNTHESIS ON -NAPHTHYLISOTHIOCYANATE-INDUCED HYPERBILIRUBINEMIA, SULFOBROMOPHTHALEIN RETENTION AND PROLONGATION OF PENTOBARBITAL HYPNOSIS

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

The effects of pretreatment with inhibitors of protein and/or ribonucleic acid synthesis such as actinomycin D, cycloheximide and ethionine on the hyperbilirubinemia, sulfobromophthalein retention and prolongation of pentobarbital narcosis induced by -naphthylisothiocyanate (ANIT) have been studied in rats. All the inhibitors studied markedly decreased or inhibited ANIT-induced hyperbilirubinemia even at doses much lower than those commonly used for the inhibition of protein and/or ribonucleic acid synthesis. None of these inhibitors had an effect on sulfobromophthalein retention when this parameter was measured 2 hours after ANIT administration. However, if sulfobromophthalein retention was assessed 24 hours after ANIT, a significant inhibition was produced by pretreatment with the inhibitors. None of the inhibitors studied had an effect on the prolongation of pentobarbital sleeping time produced by ANIT when the animals were pretreated 1 hour before ANIT. The results obtained suggest that unimpaired protein synthesis may be involved in some of the hepatotoxic effects of ANIT but not in others.