The effects of high dietary concentrations of sodium saccharin on in vivo metabolism of xenobiotics in rats

Abstract

The effect of feeding a diet containing 7.5% sodium saccharin on the conjugation of [ 14C]phenol has been studied during neonatal development in male and female rats using a two-generation protocol. Decreased formation of phenol sulphate was observed in the F 1 saccharin-treated rats from 4 wk of age and this was compensated for by an increase in the formation of quinol glucuronide. This shift in the conjugation pattern of [ 14C]phenol, with an increase in oxidation, was not sex specific. The daily excretion of indican was significantly increased from 5 wk of age. Feeding a diet containing 7.5% sodium saccharin did not affect in vitro activities of the enzymes involved in the conjugation reactions, that is, aryl sulphotransferase and uridine-5′-diphosphate glucuronyltransferase. The incorporation of 5% cysteine into the diet of saccharin-treated rats for 1 wk prevented the change in conjugation of [ 14C]phenol observed in the saccharin-treated animals. Absorption of sodium [ 35S]sulphate from the gastro-intestinal tract was not appreciably affected by a high dietary concentration of sodium saccharin. A high dietary concentration of saccharin affected the conjugation of 3-hydroxyanthranilic acid during neonatal development, possibly as a result of sulphate depletion.