Ascorbic acid requirement for the induction of microsomal drug-metabolizing enzymes in a rat mutant unable to synthesize ascorbic acid.
Ascorbic acid requirement for the induction of microsomal drug-metabolizing enzymes in a rat mutant unable to synthesize ascorbic acid.
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在无法合成抗坏血酸的突变型大鼠中，诱导微粒体药物代谢酶需要抗坏血酸。
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发表时间：
1986
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影响因子：
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通讯作者：
Y. Hayashi
中科院分区：
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作者：
F. Horio;K. Ozaki;M. Kohmura;A. Yoshida;S. Makino;Y. Hayashi
本实验研究了多氯联苯(PCBs)对不能合成抗坏血酸的突变大鼠(OD大鼠)肝脏药物代谢酶的诱导作用对抗坏血酸的需求。以能合成抗坏血酸的ods-+/+大鼠(+/+大鼠)为对照。在OD大鼠中，维持正常生长和防止任何坏疽迹象的抗坏血酸的饮食需求为每公斤饮食约300毫克抗坏血酸。在本研究中，所测试的抗坏血酸水平分别为每公斤饲料中添加或不添加200毫克多氯联苯的0、50、300、1000和3000毫克抗坏血酸。饲喂多氯联苯对上述两种基因型大鼠的生长发育均无影响。在饲喂不含多氯联苯的饲料组内进行统计分析时，抗坏血酸缺乏导致体重增加、肝脏药物代谢酶活性和肝脏细胞色素P-450水平显著下降。当OD大鼠饲喂不含多氯联苯的饲料时，每公斤饲料中添加约300 mg的抗坏血酸，足以维持肝脏氨基比林N-脱甲基酶、苯胺羟基酶、细胞色素c还原酶的正常活性，以及细胞色素P-450的减少和肝细胞色素P-450的正常水平。而在每公斤饲料中添加200 mg多氯联苯时，每公斤饲料中添加1000 mg或3000 mg抗坏血酸的OD大鼠，其肝脏氨基比林N-脱甲基酶和苯胺羟基酶活性及肝细胞色素P-450水平显著高于添加300 mg抗坏血酸的饲料。结论是，为了最大限度地诱导肝脏药物代谢，给予异物如多氯联苯可使抗坏血酸的膳食需要量增加几倍。
We investigated the requirement of ascorbic acid for the induction by polychlorinated biphenyls (PCB) of hepatic drug-metabolizing enzymes in ODS-od/od rat (OD rat) which is a rat mutant unable to synthesize ascorbic acid. ODS- +/+ rats (+/+ rat), which can synthesize ascorbic acid, were used as controls. In OD rats, the dietary requirement of ascorbic acid to maintain normal growth and prevent any signs of scurvy is about 300 mg of ascorbic acid per kilogram diet. In this study, dietary levels of ascorbic acid tested were 0, 50, 300, 1000 and 3000 mg ascorbic acid per kilogram diet with or without 200 mg of PCB per kilogram diet. Feeding PCB did not affect growth in rats of either genotype. When statistical analysis was done within groups fed diets without PCB, ascorbic acid deficiency caused significant decreases in body weight gain, hepatic activities of drug-metabolizing enzymes and level of hepatic cytochrome P-450. When OD rats were fed a diet without PCB, the supplementation of about 300 mg ascorbic per kilogram diet was sufficient to maintain normal activities of hepatic aminopyrine N-demethylase, aniline hydroxylase, cytochrome c reductase and reduction of cytochrome P-450 and a normal level of hepatic cytochrome P-450. However, when OD rats were fed a diet supplemented with 200 mg PCB per kilogram of diet, significantly higher activities of hepatic aminopyrine N-demethylase and aniline hydroxylase and significantly higher level of hepatic cytochrome P-450 were observed in OD rats fed a diet supplemented with 1000 mg or 3000 mg ascorbic acid per kilogram of diet than in rats fed a diet supplemented with 300 mg of ascorbic acid. It is concluded that the dietary requirement of ascorbic acid is increased severalfold by the administration of xenobiotics, such as PCB, for the maximum induction of hepatic drug metabolism.