p-Nitrophenol hydroxylation. A microsomal oxidation which is highly inducible by ethanol.
p-Nitrophenol hydroxylation. A microsomal oxidation which is highly inducible by ethanol.
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发表时间：
1985-09
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通讯作者：
L. A. Reinke;M. J. Moyer
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作者：
L. A. Reinke;M. J. Moyer
对硝基苯酚被广泛地用作研究葡萄糖醛酸化物和硫酸盐结合途径的底物。然而，在乙醇处理大鼠的灌流肝脏中，对-硝基苯酚被迅速代谢为4-硝基邻苯二酚。生成的4-硝基邻苯二酚与对-硝基苯酚竞争与葡萄糖醛酸和硫酸盐的结合，干扰了对-硝基苯酚的直接光谱测定。在分离的微粒体中，慢性乙醇处理后，对硝基苯酚羟化速率增加了6倍。用苯巴比妥(增加70%)或β-萘黄酮预处理(增加30%)后，可观察到较小的诱导量。此外，长期乙醇处理后，对硝基苯酚羟化速率增加6倍，大于观察到的苯胺、7-乙氧基香豆素、苯并(A)芘、乙醇或氨基比林微粒体代谢活性的增加。这些数据表明，对硝基苯酚可能是研究乙醇处理引起的药物代谢活性变化的一种非常有用的底物。
p-Nitrophenol is widely employed as a substrate for the study of the glucuronide and sulfate conjugation pathways. However, in perfused livers from ethanol-treated rats, p-nitrophenol was rapidly metabolized to 4-nitrocatechol. The 4-nitrocatechol formed competed with p-nitrophenol for conjugation with glucuronic acid and sulfate, and interfered with the direct spectral measurement of p-nitrophenol. In isolated microsomes, rates of p-nitrophenol hydroxylation were increased 6-fold after chronic ethanol treatment. Much smaller induction was observed after pretreatment of rats with phenobarbital (70% increase) or beta-naphthoflavone (30% increase). In addition, the 6-fold increase in rates of p-nitrophenol hydroxylation after chronic ethanol treatment was greater than increases in activity observed for the microsomal metabolism of aniline, 7-ethoxycoumarin, benzo(a)pyrene, ethanol, or aminopyrine. These data demonstrate that p-nitrophenol may be an extremely useful substrate for the study of changes in drug-metabolizing activity induced by ethanol treatment.