Willson R A, Hart F E
Res Commun Chem Pathol Pharmacol. 1977 Jan;16(1):59-71.
Experimental hepatic necrosis was induced in phenobarbital pretreated rats by means of the intraperitoneal administration of an acetaminophen-dimethyl sulfixide (DMSO) mixture. Cytochrome P-450 content and the specific activities of aminopyrine demethylase, aniline hydroxylase and bilirubin glucuronyl transferase diminished over the three-day study period, as compared with control animals. The reductions, however, were generally modest; not uniform for all the enzymes assayed; and correlated poorly with histologic necrosis and standard liver function tests. It is concluded that in acute liver disease changes in the hepatic in vitro drug metabolizing enzyme capacity may not be closely related to cellular necrosis, per se, and the degree of change in enzyme activities will vary from one enzyme system to another. These findings may explain, in part, the often inconsistent alterations in the disposition and elimination of drugs described in associated liver disease.
通过腹腔注射对乙酰氨基酚 - 二甲基亚砜（DMSO）混合物，在苯巴比妥预处理的大鼠中诱导实验性肝坏死。与对照动物相比，在为期三天的研究期间，细胞色素P - 450含量以及氨基比林脱甲基酶、苯胺羟化酶和胆红素葡萄糖醛酸转移酶的比活性均降低。然而，这些降低通常较为适度；对所有测定的酶而言并不一致；并且与组织学坏死和标准肝功能测试的相关性较差。得出的结论是，在急性肝病中，肝脏体外药物代谢酶能力的变化可能与细胞坏死本身并无密切关系，并且酶活性的变化程度在不同的酶系统之间会有所不同。这些发现可能部分解释了在相关肝病中所描述的药物处置和消除方面经常出现的不一致变化。
