The differential localization of various drug metabolizing systems within the rat liver lobule as determined by the hepatotoxins allyl alcohol, carbon tetrachloride and bromobenzene.
The differential localization of various drug metabolizing systems within the rat liver lobule as determined by the hepatotoxins allyl alcohol, carbon tetrachloride and bromobenzene.
复制标题
由肝毒素烯丙醇、四氯化碳和溴苯确定的大鼠肝小叶内各种药物代谢系统的差异定位。
DOI：
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发表时间：
1981
影响因子：
3.5
通讯作者：
R. Branch
中科院分区：
文献类型：
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作者：
R. James;P. Desmond;A. Küpfer;S. Schenker;R. Branch
用烯丙醇、四氯化碳或溴苯对大鼠进行预处理，诱导门脉周围、中间带至小叶中心和小叶中心肝坏死的组织病理学证据。坏死后存在的各种药物代谢酶系统的量通过测量体外特定底物的代谢速率来间接确定。这些毒素的化学诱导的肝细胞损伤在肝脏药物代谢中产生可变但显著的改变。酶活性的变化与每种毒素产生的病变面积密切相关。因此，这些肝毒素似乎是有用的探针，以确定肝小叶分布的各种药物代谢酶系统的研究。苯胺羟化酶和p-硝基苯甲醚O-脱甲基酶集中在中间带和门静脉周围带，而氨基比林N-脱甲基酶沿着细胞色素P-450梯度分布更均匀。葡萄糖醛酸转移酶在门脉周围-中间带区域更集中，乙酰转移酶在小叶中心-中间带区域，谷胱甘肽转移酶集中在中间带区域。因此，与细胞色素P-450的情况一样，肝小叶内所有药物代谢酶似乎都具有高度的区域组织性。
Rats were pretreated with allyl alcohol, carbon tetrachloride or bromobenzene to induce histopathological evidence of periportal, midzonal to centrilobular, and centrilobular hepatic necrosis. The amount of various drug metabolizing enzyme systems present after necrosis was determined indirectly by measuring the rate of metabolism for specific substrates in vitro. The chemically induced hepatocellular injury of these toxins produced variable but significant alterations in hepatic drug metabolism. The changes in enzymatic activity related well with the area of the lesion produced by each toxin. Thus, these hepatotoxins appear to be useful as probes to determine the hepatolobular distribution of the various drug metabolizing enzyme systems studied. Aniline hydroxylase and p-nitroanisole o-demethylase were concentrated in the midzonal and periportal zones, while aminopyrine N-demethylase was more uniformly distributed along the cytochrome P-450 gradient. Glucuronyltransferase was more heavily concentrated in the periportal-midzonal area, acetyltransferase was centrilobular-midzonal and glutathionetransferase was concentrated in the midzonal region. Thus, as is the case for cytochrome P-450, there appears to be a high degree of regional organization for all of the drug metabolizing enzymes within the hepatic lobule.