Pharmacokinetic analysis in serum of genistein administered subcutaneously to neonatal mice
Pharmacokinetic analysis in serum of genistein administered subcutaneously to neonatal mice
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DOI：
10.1016/s0304-3835(02)00200-8
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发表时间：
2002-10-08
期刊：
影响因子：
9.7
通讯作者：
Newbold, RR
中科院分区：
文献类型：
--
作者：
Doerge, DR;Twaddle, NC;Newbold, RR
染料木黄酮，主要的大豆异黄酮，先前被证明在出生后1-5天皮下注射后，在18个月大的雌性CD-1小鼠中诱导子宫腺癌。对相同处理的雄性和雌性小鼠的染料木素血清药代动力学分析表明：雌性（6.8 +/- 1.4 muM）和雄性（3.8 +/- 1.1 muM，平均+/- SD）中染料木素总（共轭+苷元）的最大浓度与先前报道的成年大鼠或食用大豆配方的人类婴儿的饮食暴露相当；作为活性苷元存在的平均比例（31%）与胎盘和哺乳期暴露的胎儿和新生大鼠相似；与老鼠（3到7倍）和成年人（2到3倍）相比，消除一半的时间更长。这些结果与染料木素酶偶联能力下降一致，基于个体发生，作为新生小鼠雌激素性的重要决定因素。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
Genistein, the principal soy isoflavone, was Previously shown to induce uterine adenocarcinomas by 18 months of age in female CD-1 mice following administration by subcutaneous injections on postnatal days 1-5. A serum pharmacokinetic analysis of genistein in male and female mice treated identically showed that: maximal concentrations of total (conjugated + aglycone) genistein in females (6.8 +/- 1.4 muM) and males (3.8 +/- 1.1 muM, mean +/- SD) were comparable to those previously reported from dietary exposures in adult rats or in human infants consuming soy formulas; the average fraction present as active aglycone (31%) was similar to those in fetal and neonatal rats from placental and lactational exposures; and elimination half-times were longer than those in rats (three- to seven-fold) and adult humans (two- to three-fold). These results are consistent with a diminished capacity for enzymatic conjugation of genistein, based on the ontogeny, as an important determinant of estrogenicity in neonatal mice. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.