Contrastic effects of ethionine and carbontetrachloride on ascorbic acid metabolism and on the activity of microsomal drug-metabolizing enzymes in rats.

Abstract

It is well known that the administration of chloretone, phenobarbital or methylcholanthrene induces an increase in the urinary excretion of ascorbic acid and they also induce an increase in the activities of drug-metabolizing enzyme of liver microsomes (1-3). These results indicate that there may be some relationships in the increase in the activities of microsomal drug-metabolizing enzymes and the increase in the urinary excretion of ascorbic acid. The increased activities of microsomal drug-metabolizing enzymes are prevented by the joint administration of ethionine (4-6). However, in a previous work, Kato et al. presented the evidence that the increase in the urinary excretion of ascorbic acid after the administration of chloretone or phenobarbital was not prevented by the joint administration of ethionine which completely prevented the increase in the activities of microsomal drug-metabolizing enzymes (7). These results were not in accord with the results presented by Tuoster et al. which the increased urinary excretion by chloretone or barbital is prevented by the joint administration of ethionine (8). One of the purpose of the present studies, therefore, is to reinvestigate the effect of ethionine on the increase in the urinary excretion of ascorbic acid induced by chloretone, phenobarbital or methylcholanthrene in comparison with the effect of carbontetrachloride. On the other hand, in these studies Kato et al. observed an increase in the urinary excretion of ascorbic acid after the administration of ethionine, while the administration of carbontetrachloride markedly depress the urinary excretion of ascorbic acid. The both drugs are well known hepatotoxic agents, therefore the administration of ethionine must decrease the biosynthesis of ascorbic acid and, thus it should decrease the urinary excretion of ascorbic acid. The second purpose of the present studies, therefore, is to elucidate the mechanism by which ethionine produces the increased excretion of ascorbic acid into urine. The evidence was given that ethionine could not prevent the increase in the urinary excretion of ascorbic acid induced by chloretone, phenobarbital or methylcholanthrene with the doses which almost completely prevented the increase in the activities of microsomal drug-metabolizing enzymes. On the other hand, the administration of carbontetrachloride markedly prevented the increase in the urinary excretion of ascorbic acid induced by the drugs with the doses which only partially prevents the increase in the activities of microsomal drug-metabolizing enzymes. Futheremore, ethionine decreased the liver content of ascorbic acid and thus increased the urinary excretion, while carbontetrachloride decreased the urinary excretion probably through a decrease in the ascorbic acid biosynthesis.