LONG-TERM STUDIES ON CHEMICALLY-INDUCED LIVER ENLARGEMENT IN RAT .1. SUSTAINED INDUCTION OF MICROSOMAL-ENZYMES WITH ABSENCE OF LIVER-DAMAGE ON FEEDING PHENOBARBITONE OR BUTYLATED HYDROXYTOLUENE
LONG-TERM STUDIES ON CHEMICALLY-INDUCED LIVER ENLARGEMENT IN RAT .1. SUSTAINED INDUCTION OF MICROSOMAL-ENZYMES WITH ABSENCE OF LIVER-DAMAGE ON FEEDING PHENOBARBITONE OR BUTYLATED HYDROXYTOLUENE
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DOI：
10.1016/0300-483x(77)90049-x
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发表时间：
1977-01-01
期刊：
影响因子：
4.5
通讯作者：
PARKE, DV
中科院分区：
文献类型：
--
作者：
CRAMPTON, RF;GRAY, TJB;PARKE, DV
作为肝脏增大、药物代谢酶诱导和某些形式的肝损伤之间关系研究的一部分，对饲喂含0.4%丁基羟基甲苯（BHT）或0.25%苯巴比妥的饲料长达80周的雌性大鼠肝脏进行了连续的生化和形态学观察。这两种化合物均能增加肝脏相对重量，显著提高乙基吗啡N-脱甲基酶、苯胺4-羟化酶、联苯4-羟化酶和NADPH-细胞色素c还原酶的活性以及细胞色素P-450、b5和微粒体蛋白的含量。这些变化在治疗1周后明显，并持续到80周后停止治疗。整个治疗期间观察到的唯一形态学变化是小叶中心细胞增大和滑面内质网（SER）肥大。组织化学检查显示小叶中心葡萄糖-6-磷酸酶降低，但溶酶体的正常小管周围分布没有受到干扰。在第80周停止给药后，观察到的任一化合物的所有变化均可逆。伴随药物代谢酶诱导的肝脏增大显然代表了一种适应性反应，并为解释不伴随药物代谢酶诱导的肝脏增大中发生的病理变化提供了基础。
As part of a study on the relationships between liver enlargement, induction of drug-metabolizing enzymes and certain forms of liver damage, sequential biochemical and morphological observations were made on the livers of female rats fed diets containing 0.4% butylated hydroxytoluene (BHT) or 0.25% phenobarbitone for periods of up to 80 wk. Both compounds increased the relative liver weight and produced marked enhancement of the activities of ethylmorphine N-demethylase, aniline 4-hydroxylase, biphenyl 4-hydroxylase and NADPH-cytochrome c reductase and the contents of cytochromes P-450 and b5 and microsomal protein. These changes were evident after 1 wk of treatment and persisted until treatment was stopped after 80 wk. The only morphological changes observed throughout the period of treatment were centrilobular cell enlargement and hypertrophy of the smooth endoplasmic reticulum (SER). Histochemical examination revealed a centrilobular depression of glucose-6-phosphatase but there was no disturbance of the normal pericanalicular distribution of lysosomes. All changes observed with either compound were reversible on cessation of treatment at wk 80. Liver enlargement accompanied by induction of drug-metabolizing enzymes apparently represents an adaptive response and provides a basis for the interpretation of pathological changes developing in the enlarged liver unaccompanied by drug-metabolizing enzyme induction.