Mori T, Kitamura R, Imaoka S, Funae Y, Kitada M, Kamataki T
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Res Commun Chem Pathol Pharmacol. 1992 Feb;75(2):209-19.
The content of cytochrome P-450 in liver microsomes from guinea pigs was decreased by ascorbic acid-deficiency. Since ascorbic acid is an antioxidant in vivo, the possible involvement of lipid peroxidation in this phenomenon was investigated. In fact, the level of lipid peroxides in liver homogenates of guinea pigs was increased by ascorbic acid deficiency. The level was significantly decreased when the animals were given tocopherol acetate (25 mg/kg/day, s.c.) with an ascorbic acid-free diet. The activities of aminopyrine N-demethylase, aniline hydroxylase, p-nitroanisole O-demethylase and 7-ethoxycoumarin O-deethylase, and the content of cytochrome P-450 spectrally determined did not restore the control level by the administration of tocopherol acetate to the ascorbic acid-deficient animals. Western blot analysis of liver microsomes with antibodies to rat P-450IA2 (P-448-H), P-450IIB1 (P-450b) and human P-450IIIA4 (P-450NF) showed that ascorbic acid-deficiency resulted in a decrease in the amount of cytochrome P-450 immunochemically related to P-450IA2, but not the amounts of the forms of cytochrome P-450 cross-reactive with antibodies to P-450IIB1 and P-450IIIA4. The reduced amounts of cytochrome P-450 cross-reactive with antibodies to rat P-450IA2 in liver microsomes of ascorbic acid-deficient animals remained unchanged even when lipid peroxidation was inhibited by tocopherol acetate, suggesting that there is a mechanism(s) other than lipid peroxidation involved in the reduction of amounts of cytochrome P-450 by ascorbic acid deficiency.
豚鼠肝脏微粒体中细胞色素P - 450的含量因抗坏血酸缺乏而降低。由于抗坏血酸是体内的一种抗氧化剂，因此研究了脂质过氧化在这一现象中可能的作用。事实上，抗坏血酸缺乏会使豚鼠肝脏匀浆中脂质过氧化物的水平升高。当给动物喂食无抗坏血酸饮食并皮下注射醋酸生育酚（25毫克/千克/天）时，该水平显著降低。给予抗坏血酸缺乏的动物醋酸生育酚后，氨基比林N - 脱甲基酶、苯胺羟化酶、对硝基苯甲醚O - 脱甲基酶和7 - 乙氧基香豆素O - 脱乙基酶的活性以及通过光谱测定的细胞色素P - 450的含量并未恢复到对照水平。用针对大鼠P - 450IA2（P - 448 - H）、P - 450IIB1（P - 450b）和人P - 450IIIA4（P - 450NF）的抗体对肝脏微粒体进行蛋白质免疫印迹分析表明，抗坏血酸缺乏导致与P - 450IA2免疫相关的细胞色素P - 450量减少，但与P - 450IIB1和P - 450IIIA4抗体交叉反应的细胞色素P - 450形式的量并未减少。即使醋酸生育酚抑制了脂质过氧化，抗坏血酸缺乏动物肝脏微粒体中与大鼠P - 450IA2抗体交叉反应的细胞色素P - 450减少量仍保持不变，这表明除脂质过氧化外，还有其他机制参与了抗坏血酸缺乏导致的细胞色素P - 450量的减少。
