Daidzein: Bioavailability, potential for reproductive toxicity, and breast cancer chemoprevention in female rats
Daidzein: Bioavailability, potential for reproductive toxicity, and breast cancer chemoprevention in female rats
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DOI：
10.1093/toxsci/65.2.228
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发表时间：
2002-02-01
影响因子：
3.8
通讯作者：
Eltoum, IE
中科院分区：
文献类型：
--
作者：
Lamartiniere, CA;Wang, J;Eltoum, IE
含有植物雌激素的大豆产品作为促进健康的饮食成分受到了极大的关注。大豆苷元是大豆中的一种异黄酮类和植物雌激素成分，研究了其对雌性大鼠生殖道的影响和对生殖道的发育毒性，对乳腺进行化学预防，并研究其生物利用度。以含0 mg、250 mg(低剂量)和1000 mg(高剂量)大豆苷元/kg饲料的饲料喂养未成年雌性大鼠，从繁殖前2周开始，一直持续到子代出生后50天。结果表明，饲喂低大豆苷元饲料和高大豆苷元饲料的成年雌性大鼠的血清大豆苷元浓度分别是食用高大豆传统饮食的亚洲人血清大豆苷元浓度的6倍和13倍。两种剂量的大豆苷元对小鼠的生育力、雌雄后代数量和肛门发育距离均无显著影响。大豆苷元的高剂量，而不是低剂量，导致体重减轻，这一事实可能是由于饲料消耗的减少。高大豆苷元饮食，但不是低大豆苷元饮食，循环孕酮水平，而不是雌激素水平，在统计上是降低的。两种剂量的大豆苷元对卵巢和子宫重量以及乳腺大小都有轻微的减轻作用，但不显著。对围产期暴露于大豆苷元的50天龄雌性后代生殖道的组织形态分析没有发现在阴道、子宫、卵巢和乳腺组织中有任何病理改变。围产期雌性子代暴露于250毫克大豆苷元/公斤饮食中，不会改变50天二甲基苯并(A)菲治疗大鼠的乳腺发育或化学诱导的乳腺肿瘤的个体发育。在低剂量饲粮下，妊娠、7日龄、21日龄和50日龄雌性仔猪血液中的总马酚和大豆苷元浓度分别为529和303 nM、163和982 nM、1188和1359 nM、3826和630 nM。在高大豆苷元饲料条件下，妊娠、7日龄、21日龄和50日龄雌性仔鱼血液中的马酚和大豆苷元浓度分别为4462和407 nM，1013和3841 nM，6472和3308 nM，7228和1430 nM。89%~99%的大豆苷元和马儿酚以偶联形式存在。21日龄时，高、低大豆苷元饲喂组的马酚和大豆苷元总血药浓度分别为59和34 nM，358和132 nM。低大豆苷元饲料和高大豆苷元饲料喂养7日龄大鼠乳汁中的大豆苷元几乎全部是非结合的，分别为2.6um和7.3um。总乳马醇浓度分别为654 NM和3.8微米，其中94%和44%是未结合的。7日龄仔鼠乳腺中的大豆苷元总量为407 NM(98%苷元)。我们的结论是，通过饮食给予超生理浓度的大豆苷元不会对女性生殖道造成明显的毒性，也不会对化学诱导的乳腺癌产生保护作用。
Soy products containing phytoestrogens have received much attention as dietary components to promote better health. Daidzein, an isoflavone and phytoestrogen component of soy, was investigated for its potential to alter fertility and cause developmental toxicity to the reproductive tract in female rats, for chemoprevention to the mammary gland, and to study its bioavailability. Diets containing 0 mg, 250 mg (low dose), and 1000 mg (high dose) daidzein/kg feed were fed to virgin female rats, starting 2 weeks prior to breeding and continued until the offspring were 50 days postpartum. The serum daidzein concentrations in adult female rats fed the low and high daidzein-containing diets were determined to be 6- and 13-fold higher than serum daidzein concentrations of Asians eating a traditional diet high in soy. Both daidzein doses had no significant effect on fertility, numbers of male and female offspring, and anogenital distances. The high, but not the low, daidzein dose resulted in reduced body weight, a fact that may be explained by reduced feed consumption. Circulating progesterone, but not estrogen, levels were statistically reduced with the high, but not low daidzein-containing diet. Both daidzein doses resulted in slight, but not significant, decreases in ovarian and uterine weights, and mammary gland size. Histomorphological analysis of the reproductive tracts of female offspring 50 days of age exposed perinatally to daidzein did not reveal any pathology in the vaginal, uterine, ovarian, and mammary tissues. Perinatal exposure of female offspring to 250 mg daidzein/kg diet did not alter mammary gland development or ontogeny of chemically induced mammary tumors in rats treated with dimethylbenz(a)anthracene on day 50. With the low dietary daidzein dose, total equol (major metabolite) and daidzein concentrations in the blood of pregnant females, 7-day-old, 21-day-old, and 50-day-old female offspring were 529 and 303 nM, 163 and 982 nM, 1188 and 1359 nM, and 3826 and 630 nM, respectively. With the high daidzein diet, equol and daidzein concentrations in the blood of pregnant females, 7-day-old, 21-day-old, and 50-day-old female offspring were 4462 and 407 nM, 1013 and 3841 nM, 6472 and 3308 nM, and 7228 and 1430 nM, respectively. Eighty-nine to 99% of daidzein and equol were in the conjugated form. In the 21-day-old postconceptus exposed to the low and high daidzein diets, total equol and daidzein blood concentrations were 59 and 34 nM, and 358 and 132 nM, respectively. Virtually all of the daidzein in the milk of 7-day-old rats exposed to the low and high daidzein-containing diet were unconjugated, 2.6 muM and 7.3 muM, respectively. Total milk equol concentrations were 654 nM and 3.8 muM, of which 94% and 44% were unconjugated. In mammary glands of 7-day-old offspring exposed to 250 mg daidzein/kg diet, total daidzein concentrations were 407 nM (98% aglycone). We conclude that supraphysiological concentrations of daidzein administered via the diet did not cause significant toxicity to the female reproductive tract or provide a protective effect against chemically induced mammary cancer.