The effects of high dietary concentrations of saccharin on in vitro metabolism of xenobiotics in rats.
The effects of feeding male rats a diet containing 7.5% sodium saccharin on drug metabolism in vitro were studied using both one- and two-generation protocols. Saccharin administration did not affect the hepatic concentrations of total cytochrome P-450, cytochrome b5, cytochrome P-450 reductase, aryl hydrocarbon hydroxylase activity or glutathione content but caused a statistically significant increase in dimethylnitrosamine-N-demethylase activity. This increase was detectable in neonatal animals treated using a two-generation protocol. Administration of the sodium, potassium or calcium salts of saccharin or its acid form at 5% in the diet to male rats for 8 wk each caused a significant increase in dimethylnitrosamine-N-demethylase activity. Fasting control and saccharin-treated male rats for 24 hr before the dimethylnitrosamine-N-demethylase assay increased the activity of this enzyme in both groups slightly. The observed increase in dimethylnitrosamine-N-demethylase activity recorded in both male and female rats fed diets containing saccharin after 8 to 12 wk of treatment was reversed when the animals were given control diet for 4 wk.
Heaton
G D
GD
Clinical Pharmacology Group, University of Southampton, UK.
Renwick
A G
AG
D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004032:Diet; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin / Q000008:administration & dosage / Q000633:toxicity*; D001743:Urinary Bladder / Q000187:drug effects
D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; D000123:Acetyltransferases; D012439:Saccharin