Kamisako T, Adachi Y, Yamamoto T
Second Department of Internal Medicine, Kinki University School of Medicine, Osaka, Japan.
J Pharmacol Exp Ther. 1990 Aug;254(2):380-2.
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.
为了确定UDP-葡萄糖醛酸（UDPGA）耗竭对胆红素代谢的影响，将水杨酰胺（SAM，主要通过葡萄糖醛酸化代谢）以2 mmol/kg的剂量给予大鼠，并测定胆汁胆红素排泄及胆红素葡萄糖醛酸酯的比例。给予SAM后15分钟，肝脏中的UDPGA水平显著降低。尽管胆汁中胆红素的总排泄量没有变化，但给予SAM后0至30分钟期间，胆红素二葡萄糖醛酸酯水平显著低于同期未处理的对照组（36.9±4.3% 对比47.5±1.7%；P<0.01）。与对照组相比，0至30分钟期间胆汁中胆红素单葡萄糖醛酸酯（BMG）水平显著升高。0至30分钟期间C8-BMG/C12-BMG比值显著高于对照组。给予SAM后150分钟，肝脏中UDPGA水平升高，同时胆红素二葡萄糖醛酸酯增加，BMG减少。这些结果表明，给予SAM导致肝脏中UDPGA的变化影响胆汁中胆红素的组成。
