Inhibition of pancreatic cholesterol esterase reduces cholesterol absorption in the hamster.
Inhibition of pancreatic cholesterol esterase reduces cholesterol absorption in the hamster.
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DOI：
10.1186/1471-2210-4-5
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发表时间：
2004-04-19
期刊：
影响因子：
--
通讯作者：
Vander Jagt DL
中科院分区：
文献类型：
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作者：
Heidrich JE;Contos LM;Hunsaker LA;Deck LM;Vander Jagt DL
胰腺胆固醇酯酶在肠道中具有三种功能：1）控制来自膳食胆固醇酯的胆固醇的生物利用度; 2）有助于胆固醇掺入混合胶束; 3）帮助游离胆固醇转运至肠上皮细胞。预期胆固醇酯酶抑制剂可限制膳食胆固醇的吸收。将选择性和有效的胆固醇酯酶抑制剂6-氯-3-（1-乙基-2-环己基）-2-吡喃酮（图1，结构1）给予喂食补充有放射性标记的胆固醇酯的高胆固醇饮食的仓鼠。用管饲法给仓鼠喂饲3 H标记的油酸胆固醇酯沿着抑制剂1.0 -200微摩尔。24小时后，测定肝脏和血清放射性胆固醇水平。抑制剂1用于防止由标记的胆固醇油酸酯的水解衍生的标记的胆固醇的摄取的ED 50为100微摩尔。在30天饲养试验中研究抑制剂1的毒性。将抑制剂1（每天100微摩尔或200微摩尔）添加到补充有1%胆固醇和0.5%胆酸的食物中。获得临床化学、尿分析和组织病理学结果。在对照组和抑制剂补充组之间没有观察到毒性差异。胆固醇酯酶抑制剂可能是限制胆固醇吸收的有用治疗剂。
Pancreatic cholesterol esterase has three proposed functions in the intestine: 1) to control the bioavailability of cholesterol from dietary cholesterol esters; 2) to contribute to incorporation of cholesterol into mixed micelles; and 3) to aid in transport of free cholesterol to the enterocyte. Inhibitors of cholesterol esterase are anticipated to limit the absorption of dietary cholesterol. The selective and potent cholesterol esterase inhibitor 6-chloro-3-(1-ethyl-2-cyclohexyl)-2-pyrone (figure 1, structure 1) was administered to hamsters fed a high cholesterol diet supplemented with radiolabeled cholesterol ester. Hamsters were gavage fed 3H-labeled cholesteryl oleate along with inhibitor 1, 0–200 micromoles. Twenty-four hours later, hepatic and serum radioactive cholesterol levels were determined. The ED50 of inhibitor 1 for prevention of the uptake of labeled cholesterol derived from hydrolysis of labeled cholesteryl oleate was 100 micromoles. The toxicity of inhibitor 1 was investigated in a 30 day feeding trial. Inhibitor 1, 100 micromoles or 200 micromoles per day, was added to chow supplemented with 1% cholesterol and 0.5% cholic acid. Clinical chemistry urinalysis and tissue histopathology were obtained. No toxicity differences were noted between control and inhibitor supplemented groups. Inhibitors of cholesterol esterase may be useful therapeutics for limiting cholesterol absorption.