Khanduja K L, Koul A, Koul I B, Gupta M P
Biochem Int. 1986 Oct;13(4):659-70.
Water solubility and non-toxic properties of ascorbic acid are taken as criteria for beneficial effects of large doses of the vitamin. In the present study, male guinea pigs, dosed daily with 15, 30 or 50 mg/100g body weight for 10 weeks, demonstrated no differences in effect on liver and lung weights, body growth and microsomal protein contents of liver and lung when compared with controls. When guinea pigs were fed excessive ascorbic acid, there was a small non-significant increase (p less than 0.05) in hepatic and pulmonary cytochrome P-450, and significant increase (p less than 0.05) in hepatic cytochrome b5 which was accompanied with a significant increase in arylhydrocarbon hydroxylase activity in the two organs. Activity of NADPH-dependent cytochrome c-reductase was decreased in liver and remained unaffected in lung and colon. Drug detoxifying enzymes responded in different ways to increased intake of ascorbic acid. Activity of UDP-glucuronyltransferase remained unchanged on feeding excessive ascorbic acid, whereas glutathione S-transferase was decreased significantly in liver and was unaltered in lung and colon. Reduced glutathione was decreased only in the lung. The observed changes in drug activating and detoxifying enzymes appear to be important from drug pharmacokinetics and carcinogenesis point of view.
维生素C的水溶性和无毒特性被视为大剂量该维生素产生有益作用的标准。在本研究中，雄性豚鼠每天按15、30或50毫克/100克体重的剂量给药，持续10周，与对照组相比，在肝脏和肺脏重量、身体生长以及肝脏和肺脏微粒体蛋白含量方面未显示出差异。当豚鼠摄入过量维生素C时，肝脏和肺脏中的细胞色素P-450有小幅但无统计学意义的增加（p小于0.05），肝脏细胞色素b5有显著增加（p小于0.05），同时这两个器官中的芳烃羟化酶活性也显著增加。肝脏中依赖NADPH的细胞色素c还原酶活性降低，而肺脏和结肠中的该活性未受影响。药物解毒酶对维生素C摄入量增加的反应各不相同。摄入过量维生素C时，尿苷二磷酸葡萄糖醛酸基转移酶活性保持不变，而肝脏中的谷胱甘肽S-转移酶显著降低，肺脏和结肠中的该酶活性未改变。仅肺脏中的还原型谷胱甘肽减少。从药物药代动力学和致癌作用的角度来看，所观察到的药物激活和解毒酶的变化似乎很重要。
