The effects of high dietary concentrations of sodium saccharin on in vivo metabolism of xenobiotics in rats.
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 F1 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.
Heaton
G D
GD
Clinical Pharmacology Group, University of Southampton, UK.
Renwick
A G
AG
D015095:3-Hydroxyanthranilic Acid / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D015239:Arylsulfotransferase / Q000378:metabolism; D003545:Cysteine / Q000494:pharmacology; D004032:Diet; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D008297:Male; D019800:Phenol; D010636:Phenols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin / Q000008:administration & dosage / Q000494:pharmacology*; D013431:Sulfates / Q000493:pharmacokinetics* / Q000652:urine; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D006025:Glycosaminoglycans; D010636:Phenols; D013431:Sulfates; C012036:sodium sulfate; D015095:3-Hydroxyanthranilic Acid; D019800:Phenol; D014453:Glucuronosyltransferase; D015239:Arylsulfotransferase; D012439:Saccharin; D003545:Cysteine