Diminished rates of glucuronidation and sulfation in perfused rat liver after chronic ethanol administration.
Diminished rates of glucuronidation and sulfation in perfused rat liver after chronic ethanol administration.
复制标题
长期给予乙醇后，灌注大鼠肝脏中葡萄糖醛酸化和硫酸化的速率降低。
DOI：
10.1016/0006-2952(86)90217-0
复制
发表时间：
1986
影响因子：
5.8
通讯作者：
Notley,KA
中科院分区：
文献类型：
--
作者：
Reinke,LA;Moyer,MJ;Notley,KA
在正常饲料喂养大鼠的灌注肝脏或喂食液体对照或含乙醇饲料的大鼠肝脏中研究了7-羟基香豆素的葡萄糖醛酸化和硫酸化速率。在输注100 μM 7-羟基香豆素期间，饲喂普通饲料或对照饲料的大鼠肝脏中的葡萄糖醛酸化速率相似，但饲喂乙醇的大鼠肝脏中的葡萄糖醛酸化速率低34%。灌流肝脏中的葡萄糖醛酸化率不能解释UDP-葡萄糖醛酸转移酶活性的变化，这是最高的乙醇处理的大鼠肝musomes和最低的musomes从饲料喂养的大鼠。乙醇处理大鼠肝脏中葡萄糖醛酸化率较低与UDP-葡萄糖醛酸的肝脏浓度较低相关，低于其他处理组中测定水平的70%。然而，UDP-葡萄糖醛酸水平的降低不能通过腺嘌呤核苷酸、NAD+/NADH比率、糖原、UDP-葡萄糖或UDP-葡萄糖脱氢酶活性的改变来解释。硫酸化率下降，在长期7-羟基香豆素输注乙醇处理的大鼠的肝脏，但不是在肝脏中接受了控制饮食。同样，仅在乙醇处理大鼠的肝脏中，腺苷-3 '-磷酸-5'-硫酸酯磷酸（PAPS）的肝脏浓度也随时间降低。因此，慢性乙醇喂养损害灌注肝脏中的葡萄糖醛酸化和硫酸化，这是由于这些缀合途径所需辅因子的可用性降低。
Rates of glucuronidation and sulfation of 7-hydroxycoumarin were studied in perfused livers from normal chow-fed rats, or in livers from rats that had been fed liquid control or ethanol-containing diets. During infusion of 100 μM 7-hydroxycoumarin, rates of glucuronidation were similar in livers from chow-fed or control diet rats, but were 34% less in livers from ethanol-fed rats. These rates of glucuronidation in perfused livers could not be explained by changes of UDP-glucuronyltransferase activity, which was highest in hepatic musomes from ethanol-treated rats and lowest in musomes from chow-fed rats. The low rates of glucuronidation in livers from ethanol-treated rats were correlated with low hepatic concentrations of UDP-glucuronic acid, which were less than 70% of the levels measured in the other treatment groups. However, the diminished UDP-glucuronic acid levels could not be explained by alterations in adenine nucleotides, NAD+/NADH ratios, glycogen, UDP-glucose, or activity of UDP-glucose dehydrogenase. Rates of sulfation declined during prolonged 7-hydroxycoumarin infusion in livers from ethanol-treated rats, but not in livers from rats that had received the control diet. Similarly, hepatic concentrations of adenosine-3'-phosphate 5'-sulfatophosphate (PAPS) also decreased with time only in livers from ethanol-treated rats. Thus, chronic ethanol feeding impairs glucuronidation and sulfation in perfused livers as a result of diminished availability of the required cofactors for these conjugation pathways.