Effect of UDP-glucuronic acid depletion by salicylamide on biliary bilirubin excretion in the rat.
To determine the effect of UDP-glucuronic acid (UDPGA) depletion on bilirubin metabolism, salicylamide (SAM, which is metabolized primarily through glucuronidation, was administered to rats at a dose of 2 mmol/kg, and biliary bilirubin excretion and the proportion of bilirubin glucuronides were determined. At 15 min after administration of SAM, the UDPGA level in the liver was markedly decreased. Although the total biliary excretion of bilirubin showed no change, the bilirubin diglucuronide level in the 0- to 30-min period after SAM administration was significantly lower (36.9 +/- 4.3%) than that of the untreated control group during the same period (47.5 +/- 1.7%; P less than .01). The biliary bilirubin monoglucuronide (BMG) level in the 0- to 30-min period was significantly increased, compared with the control group. The C8-BMG/C12-BMG ratio in the 0- to 30-min period was significantly higher than that of the control group. At 150 min after SAM administration, there was an increase in the UDPGA level in the liver accompanied by an increase in bilirubin diglucuronide and a decrease in BMG. These results indicate that changes in UDPGA in the liver due to SAM administration influence the bilirubin composition of the bile.
Kamisako
T
T
Second Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
Adachi
Y
Y
Yamamoto
T
T
D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis / Q000378:metabolism; D001663:Bilirubin / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012457:Salicylamides / Q000494:pharmacology*; D014535:Uridine Diphosphate Glucuronic Acid / Q000032:analysis / Q000172:deficiency* / Q000378:metabolism; D014539:Uridine Diphosphate Sugars / Q000172:deficiency*
D001647:Bile Acids and Salts; D012457:Salicylamides; D014539:Uridine Diphosphate Sugars; D014535:Uridine Diphosphate Glucuronic Acid; C031060:salicylamide; D001663:Bilirubin