Circadian variation of hepatic UDP-glucuronic acid and the glucuronidation of xenobiotics in mice.
A circadian cycle in hepatic UDP-glucuronic acid (UDP-GA) concentration was observed in mice that was essentially the reverse of those seen for hepatic glycogen and UDP-glucose. That is, hepatic UDP-GA levels were highest during the fasting period and lowest during the feeding period. However, there was no significant difference between the half-lives or the apparent rates of glucuronidation for either acetaminophen or salicylamide at 8 a.m. and 5 p.m. Therefore, the previously-reported circadian variation in acetaminophen toxicity is probably due to circadian variation in hepatic glutathione levels rather than in hepatic glucuronidation capacity.
Howell
S R
SR
Environmental Health and Occupational Medicine Center, University of Kansas Medical Center, Kansas City 66103.
Klaassen
C
C
D000082:Acetaminophen / Q000493:pharmacokinetics*; D000818:Animals; D002940:Circadian Rhythm; D005966:Glucuronidase / Q000378:metabolism*; D006207:Half-Life; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D012457:Salicylamides / Q000493:pharmacokinetics*; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism*; D015262:Xenobiotics / Q000493:pharmacokinetics*
D008112:Liver Glycogen; D012457:Salicylamides; D015262:Xenobiotics; D014535:Uridine Diphosphate Glucuronic Acid; D000082:Acetaminophen; D005966:Glucuronidase; C031060:salicylamide