Takashima K, Kohno T, Mori T, Ohtani A, Hirakoso K, Takeyama S
Research Laboratories, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Atherosclerosis. 1994 Jun;107(2):247-57. doi: 10.1016/0021-9150(94)90026-4.
The hypocholesterolemic property of 1-(3,4-dimethoxyphenyl)-2,3- bis(methoxycarbonyl)-4-hydroxy-6,7,8-trimethoxynaphthalene (TA-7552) and its effects on cholesterol metabolism were investigated in the rat. TA-7552 incorporated into a hypercholesterolemic diet at a concentration of 0.2% and administered for 7 days reduced serum cholesterol by 72% and liver cholesterol by 90%, and its minimal effective dose was 0.01% in the diet. Its hypocholesterolemic effect was associated with an elevation of serum HDL-cholesterol. Inclusion of 0.1% TA-7552 in the normal laboratory chow accelerated fecal excretion of 14C derived from orally administered 4-[14C]cholesterol or carbonyl-[14C]taurocholate. The net amounts of fecal neutral sterols and bile acids were markedly increased by the same treatment. Hepatic bile acid production and hepatic and intestinal cholesterol biosynthesis as measured by cholesterol 7 alpha-hydroxylase activity and 1-[14C]acetate incorporation into tissue cholesterol, respectively, were both stimulated by the drug treatment. All these data indicate that this hypocholesterolemic agent inhibits intestinal absorption of both cholesterol and bile acids and compensatorily stimulates hepatic production of bile acids and cholesterol.
研究了1-(3,4-二甲氧基苯基)-2,3-双(甲氧基羰基)-4-羟基-6,7,8-三甲氧基萘(TA-7552)的降胆固醇特性及其对大鼠胆固醇代谢的影响。将TA-7552以0.2%的浓度加入高胆固醇饮食中并给药7天，可使血清胆固醇降低72%，肝脏胆固醇降低90%，其在饮食中的最小有效剂量为0.01%。其降胆固醇作用与血清高密度脂蛋白胆固醇升高有关。在正常实验室饲料中加入0.1%的TA-7552可加速口服4-[14C]胆固醇或羰基-[14C]牛磺胆酸盐衍生的14C的粪便排泄。相同处理可使粪便中性固醇和胆汁酸的净含量显著增加。通过胆固醇7α-羟化酶活性和1-[14C]乙酸掺入组织胆固醇分别测定的肝脏胆汁酸生成以及肝脏和肠道胆固醇生物合成均受到药物治疗的刺激。所有这些数据表明，这种降胆固醇药物抑制胆固醇和胆汁酸的肠道吸收，并代偿性刺激肝脏胆汁酸和胆固醇的生成。
