Poulsen H E, Lerche A, Skovgaard L T
Biochem Pharmacol. 1985 Oct 15;34(20):3729-33. doi: 10.1016/0006-2952(85)90238-2.
The effect of a toxic dose of acetaminophen on the hepatic conjugations of acetaminophen was studied in single pass perfused livers from rats given acetaminophen overdose 12 hr prior to perfusion and from control rats. Four different acetaminophen concentrations (0.1-6 mmol/1) were used in each perfusion. Glucuronidation of acetaminophen was increased and sulfation of acetaminophen occurred at an unchanged rate in acetaminophen damaged livers as compared to control livers. Hepatic glutathione concentrations declined to about 0.4 mumol/g liver during perfusion, possibly due to excretion of glutathione to perfusion medium, but in spite of this the formation of glutathione conjugates was increased with acetaminophen concentrations increasing up to about 5 mmol. We conclude that decreased sulfation, glucuronidation and glutathione conjugation in the liver is not present in the early development of acetaminophen-induced hepatic damage.
研究了给予对乙酰氨基酚过量12小时后的大鼠单次灌注肝脏及对照大鼠肝脏中，对乙酰氨基酚的毒性剂量对其肝脏结合作用的影响。每次灌注使用四种不同的对乙酰氨基酚浓度（0.1 - 6 mmol/1）。与对照肝脏相比，对乙酰氨基酚受损肝脏中对乙酰氨基酚的葡萄糖醛酸化增加，而硫酸化速率不变。灌注期间肝脏谷胱甘肽浓度降至约0.4 μmol/g肝脏，这可能是由于谷胱甘肽排泄到灌注培养基中，但尽管如此，随着对乙酰氨基酚浓度增加至约5 mmol，谷胱甘肽结合物的形成增加。我们得出结论，在对乙酰氨基酚诱导的肝损伤早期发展过程中，肝脏中硫酸化、葡萄糖醛酸化和谷胱甘肽结合作用并未降低。
