Holloway D E, Rivers J M
J Nutr. 1981 Mar;111(3):412-24. doi: 10.1093/jn/111.3.412.
The influence of chronic ascorbic acid (AA) deficiency and excessive ascorbate consumption on bile acid metabolism, liver and plasma cholesterol levels, hepatic microsomal cytochromes and biliary lipid composition was investigated. Male weanling guinea pigs were fed a cereal-based scorbutigenic diet supplemented with four levels of AA for 7 weeks: deficient, 15 and 30 mg/kg; control, 500 mg/kg; and excess, 20,000 mg/kg. Bile acid kinetic parameters were determined following the intraperitoneal administration of [24-14C] chenodeoxycholic acid. Dietary extremes of AA caused similar alterations in the parameters studied. Relative to the control group, the deficient and excess groups exhibited reduced cytochrome P-450 concentration, lower cholesterol 7 alpha-hydroxylase activity, lower bile acid turnover rate, prolonged bile acid half-life and increased plasma and liver cholesterol concentrations. Deficient and excess groups also exhibited lower biliary cholesterol saturation (i.e., increased bile acid-neutral sterol ratios) than controls. Urinary bile acid excretion was 2- to 3-fold higher in excess guinea pigs than in the other three groups. The data demonstrate the exceptional susceptibility of cholesterol 7 alpha-hydroxylase activity to alteration by dietary extremes of AA, resulting in marked inhibition of bile acid synthesis and elevation of cholesterol levels by both inadequate and excessive AA intake.
研究了慢性抗坏血酸（AA）缺乏和过量摄入抗坏血酸盐对胆汁酸代谢、肝脏和血浆胆固醇水平、肝微粒体细胞色素以及胆汁脂质组成的影响。将雄性断奶豚鼠喂食以谷物为基础的致坏血病饮食，并补充四种水平的AA，持续7周：缺乏组，15和30毫克/千克；对照组，500毫克/千克；过量组，20,000毫克/千克。在腹腔注射[24-14C]鹅去氧胆酸后测定胆汁酸动力学参数。AA饮食的极端情况在研究参数中引起了类似的变化。相对于对照组，缺乏组和过量组表现出细胞色素P-450浓度降低、胆固醇7α-羟化酶活性降低、胆汁酸周转率降低、胆汁酸半衰期延长以及血浆和肝脏胆固醇浓度升高。缺乏组和过量组的胆汁胆固醇饱和度也低于对照组（即胆汁酸与中性固醇的比率增加）。过量组豚鼠的尿胆汁酸排泄量比其他三组高2至3倍。数据表明胆固醇7α-羟化酶活性对AA饮食极端情况的改变异常敏感，导致AA摄入不足和过量均显著抑制胆汁酸合成并升高胆固醇水平。
