Okada K, Mochizuki T, Shinohara Y, Takahashi S, Takagi K, Irikura T
Nihon Yakurigaku Zasshi. 1984 Apr;83(4):331-43.
The hypolipidemic properties of KCD-232[4-(4'-chlorobenzyloxy) benzyl nicotinate], a new compound, were studied in rats fed a basal diet and mice fed a high-cholesterol diet with the following results: KCD-232 reduced serum cholesterol (CH), triglyceride (TG) and phospholipid (PL) levels in a dose-dependent manner (20 approximately 160 mg/kg/day) in rats fasted for 16 hr. KCD-232 significantly reduced (LDL + VLDL)-CH and decreased the (LDL + VLDL)-CH/HDL-CH ratio designated as the "atherogenic index" unlike clofibrate which was used as a reference. KCD-232 slightly increased relative liver weight, but not in the dose-dependent manner of clofibrate. KCD-232 also inhibited the elevation of serum CH level in mice fed a high-cholesterol diet in a dose-dependent manner, and this inhibitory effect was more pronounced than those of clofibrate and nicotinic acid (NA). Liver CH and fatty acid (FA) synthesis from [1-14C] acetate were inhibited both in vitro and in vivo in rats orally administered KCD-232. Clofibrate also decreased CH synthesis, whereas it increased FA synthesis. NA had no effect on either synthesis. After oral administration of [4-14C] cholesterol to rats that were cannulated into the thoracic-duct lymph, KCD-232 markedly depressed the appearance of 14C-cholesterol in lymph. KCD-232 induced no proliferation of hepatic peroxisomes in rats, unlike clofibrate. The detailed hypolipidemic mechanism of KCD-232 is not yet clear, but as shown, it decreased CH synthesis in the liver, exogenous CH absorption from the intestine and FA synthesis in the liver. These results suggest that the serum lipid-lowering profiles of KCD-232 differ from those of clofibrate and NA.
对新型化合物KCD - 232[4-(4'-氯苄氧基)苄基烟酸酯]的降血脂特性进行了研究，实验对象为喂食基础饮食的大鼠和喂食高胆固醇饮食的小鼠，结果如下：在禁食16小时的大鼠中，KCD - 232以剂量依赖性方式（20至约160毫克/千克/天）降低血清胆固醇（CH）、甘油三酯（TG）和磷脂（PL）水平。与用作对照的氯贝丁酯不同，KCD - 232显著降低（低密度脂蛋白 + 极低密度脂蛋白）-CH，并降低被称为“致动脉粥样化指数”的（低密度脂蛋白 + 极低密度脂蛋白）-CH/高密度脂蛋白-CH比值。KCD - 232使相对肝脏重量略有增加，但不像氯贝丁酯那样呈剂量依赖性。KCD - 232还以剂量依赖性方式抑制喂食高胆固醇饮食小鼠的血清CH水平升高，且这种抑制作用比氯贝丁酯和烟酸（NA）更明显。口服KCD - 232的大鼠，其肝脏CH和由[1-14C]乙酸盐合成脂肪酸（FA）在体内外均受到抑制。氯贝丁酯也降低CH合成，但增加FA合成。NA对两者合成均无影响。对胸导管插管的大鼠口服[4-14C]胆固醇后，KCD - 232显著抑制淋巴中14C-胆固醇的出现。与氯贝丁酯不同，KCD - 232未诱导大鼠肝脏过氧化物酶体增殖。KCD - 232具体的降血脂机制尚不清楚，但如图所示，它降低了肝脏中的CH合成、肠道对外源性CH的吸收以及肝脏中FA的合成。这些结果表明，KCD - 232的血清降脂谱与氯贝丁酯和NA不同。
