Safety evaluation of phytosterol esters.: Part 1.: Assessment of oestrogenicity using a combination of in vivo and in vitro assays
Safety evaluation of phytosterol esters.: Part 1.: Assessment of oestrogenicity using a combination of in vivo and in vitro assays
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DOI：
10.1016/s0278-6915(98)00101-x
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发表时间：
1999-01-01
影响因子：
4.3
通讯作者：
Ashby, J
中科院分区：
文献类型：
--
作者：
Baker, VA;Hepburn, PA;Ashby, J
植物甾醇是人类饮食中的天然成分，作为广泛的安全性评估研究计划的一部分，研究了它们作为一种新型食品成分的用途，植物甾醇可能的雌激素效应已通过体外和体内试验的组合进行了研究。植物甾醇与未成熟大鼠子宫雌激素受体（ER）的竞争性结合已被用于测量其与ER的结合能力，而雌激素应答基因的转录激活已在雌激素诱导酵母筛选中进行了检测。植物甾醇在这些体外实验中没有显示出任何活性。已经进行了子宫营养试验，以研究植物甾醇在连续3天以0、5、50或500 mg/kg/天的剂量口服给药给未成熟雌性大鼠（n = 10）时引发雌激素反应的可能性。植物甾醇（谷甾醇、油菜甾醇和豆甾醇的混合物）和植物甾醇酯（之前的植物甾醇混合物与葵花籽油中的脂肪酸酯化）在未成熟雌性大鼠中没有表现出雌激素活性，以子宫湿重为终点。-雌二醇（0.4 mg/kg/天）持续显著增加子宫重量。库美特罗（一种已知的植物雌激素）也作为弱阳性对照进行了测试，并在子宫收缩试验中产生剂量反应，剂量为20,40和80mg /kg/天。总之，我们已经证明植物甾醇不会与内质网结合，也不会刺激重组酵母菌株中人内质网的转录活性。此外，未成熟雌性大鼠口服灌胃该物质时，子宫营养实验没有显示出雌激素性。1998爱思唯尔科学有限公司版权所有。
Phytosterols are natural constituents of the human diet, and as part of an extensive programme of safety evaluation studies investigating their use as a novel food ingredient, the possible oestrogenic effects of phytosterols have been investigated using a combination of in vitro and in vivo assays. Competitive binding with the immature rat uterine oestrogen receptor (ER) has been used to measure the ability of phytosterols to bind to ERs while the transcriptional activation of oestrogen-responsive genes has been examined in an oestrogen-inducible yeast screen. Phytosterols did not display any activity in these in vitro assays. Uterotrophic assays have been conducted to investigate the potential for phytosterols to elicit an oestrogenic response when administered orally to immature female rats (n = 10) at doses of 0, 5, 50 or 500 mg/kg/day for 3 consecutive days. Phytosterols (a well characterized mixture of -sitosterol, campesterol and stigmasterol) and phytosterol esters (the previous phytosterol mixture esterified with fatty acids from sunflower oil) did not exhibit oestrogenic activity in the immature female rat using uterine wet weight as the endpoint. beta-oestradiol (0.4 mg/kg/day) consistently produced a significant increase in uterus weights. Coumestrol (a known phytoestrogen) was also tested as a weak positive control and produced a dose response at doses of 20, 40 and 80 mg/kg/day in the uterotrophic assay. In conclusion, we have shown that phytosterols do not bind to the ER and do not stimulate transcriptional activity of the human ER in a recombinant yeast strain. In addition, there was no indication of oestrogenicity from the uterotrophic assay when the material was administered by oral gavage to immature female rats. (C) 1998 Elsevier Science Ltd. All rights reserved.