Peterson F J, Holloway D E, Duquette P H, Rivers J M
Biochem Pharmacol. 1983 Jan 1;32(1):91-6. doi: 10.1016/0006-2952(83)90658-5.
Studies were carried out to characterize the response of hepatic mixed function oxidase (MFO) activity to chronic ascorbic acid deficiency and excessive ascorbic acid intake in the guinea pig. When guinea pigs were fed excessive ascorbic acid, there was a small increase in hepatic cytochrome P-450 which was unaccompanied by any alteration in drug-metabolizing enzyme activity. Similarly, induction of MFO activity by phenobarbital was not modified by excessive ascorbic acid administration. Chronic ascorbic acid deficiency resulted in depressed metabolism of aniline, aminopyrine, ethoxycoumarin and benzphetamine, but not of ethylmorphine, in comparison with animals fed diets containing control and/or excessive amounts of ascorbic acid. In contrast to the metabolism of all drugs studied, the 7 alpha-hydroxylation of cholesterol was depressed by both inadequate and excessive vitamin C intake, demonstrating the unique sensitivity of cholesterol 7 alpha-hydroxylase to dietary ascorbate.
开展了多项研究,以表征豚鼠肝脏混合功能氧化酶(MFO)活性对慢性抗坏血酸缺乏和过量摄入抗坏血酸的反应。当给豚鼠喂食过量抗坏血酸时,肝脏细胞色素P - 450有小幅增加,但药物代谢酶活性未发生任何改变。同样,过量给予抗坏血酸并不会改变苯巴比妥对MFO活性的诱导作用。与喂食含有对照量和/或过量抗坏血酸日粮的动物相比,慢性抗坏血酸缺乏导致苯胺、氨基比林、乙氧香豆素和苄非他明的代谢受到抑制,但对乙基吗啡的代谢没有影响。与所研究的所有药物的代谢情况不同,维生素C摄入不足和过量均会抑制胆固醇的7α-羟化作用,这表明胆固醇7α-羟化酶对日粮抗坏血酸盐具有独特的敏感性。