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首页> 外文期刊>Archives of Toxicology >Toxicokinetics of the phytoestrogen daidzein in female DA/Han rats.
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Toxicokinetics of the phytoestrogen daidzein in female DA/Han rats.

机译：植物雌激素黄豆苷元在雌性DA / Han大鼠中的毒代动力学。

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Female DA/Han rats were given the phytoestrogen daidzein, either intravenously (10 mg/kg b.w.) or orally by gavage (10 or 100 mg/kg b.w.). The plasma concentration-time curve determined after i.v. administration of daidzein was fitted to a triexponential model, resulting in a final half-life (gamma-phase) of approximately 4 h. The oral bioavailability of 10 mg daidzein/kg was 9.7%, while that of 100 mg/kg was 2.2%; the higher dose (100 mg/kg) was apparently absorbed to a four- to fivefold lower extent than the smaller dose. The plasma concentration time curves after oral administration of daidzein to female DA/Han rats revealed pronounced interindividual differences and multiple peaks, pointing to extensive enterohepatic circulation and/or protracted absorption from the gastrointestinal tract. As shown in a separate experiment with bile duct-cannulated rats, daidzein (i.p. 10 mg/kg b.w.) is efficiently excreted with bile: glucuronide/sulfate metabolites amounting to approximately 30% of the dose in 8 h. Conjugates were also the main circulating metabolites upon i.v. or gavage administration of daidzein, indicating efficient phase II metabolism in female DA/Han rats. Since only few data have been published on tissue levels of isoflavones, their concentrations were measured in various organs and compared to plasma levels determined at the time the animals were killed, with one exception 32 or 48 h after rats had received a single dose of daidzein (i.v. or per os). As expected, the daidzein concentrations depended upon dose and administration route. Despite notable differences in the absolute amounts of total daidzein (free plus hydrolyzed conjugates), the levels were usually three- to fivefold higher in liver and kidney than in plasma; in most samples of uteri, the concentrations were similar, or up to twofold higher, than the respective plasma levels. These data point to an uptake and storage of isoflavones and metabolites in tissues. Experimental toxicokinetics appear to be a relevant subject that should be integrated into assessments of toxicological data for endocrine modulators.
机译：给雌性DA / Han大鼠静脉内（10mg / kg b.w.）或通过管饲法（10或100mg / kg b.w.）给予植物雌激素黄豆苷元。 i.v.后测定的血浆浓度-时间曲线黄豆苷元的给药适合三指数模型，导致最终半衰期（γ相）约为4小时。 10 mg大豆黄酮/ kg的口服生物利用度为9.7％，而100 mg / kg的口服生物利用度为2.2％;较高的剂量（100 mg / kg）显然比较小的剂量吸收低四到五倍。向雌性DA / Han大鼠口服黄豆苷元后的血浆浓度时间曲线显示出明显的个体差异和多个峰，表明广泛的肝肠循环和/或胃肠道吸收延长。如对胆管插管大鼠进行的另一项实验所示，黄豆苷元（ip.p. 10 mg / kg b.w.）被胆汁：葡萄糖醛酸/硫酸盐代谢物有效排泄，在8小时内约占剂量的30％。结合物也是静脉注射时主要的循环代谢产物。或强饲黄豆苷元，表明雌性DA / Han大鼠有效的II期代谢。由于只有很少的关于异黄酮组织水平的数据公开，因此在不同器官中测量了它们的浓度，并与动物被杀死时确定的血浆水平进行了比较，但大鼠接受单剂量黄豆苷元后32或48小时除外（iv或per os）。如预期的那样，大豆黄酮的浓度取决于剂量和给药途径。尽管总大豆苷元（游离加水解共轭物）的绝对量存在显着差异，但肝脏和肾脏中的水平通常比血浆中高三到五倍。在大多数子宫样本中，其浓度与各自的血浆水平相近，或高出两倍。这些数据表明异黄酮和代谢产物在组织中的吸收和储存。实验性毒物代谢动力学似乎是一个相关主题，应纳入内分泌调节剂毒理学数据评估中。

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