TERATOGENICITY OF IONIC CADMIUM IN THE WISTAR RAT
TERATOGENICITY OF IONIC CADMIUM IN THE WISTAR RAT
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DOI：
10.1007/bf00316212
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发表时间：
1987-04-01
影响因子：
6.1
通讯作者：
WEBB, M
中科院分区：
文献类型：
--
作者：
HOLT, D;WEBB, M
在本发明（重新衍生的）Wistar-Porton 品系的大鼠中，在妊娠第 12 天（gd 12）静脉内（i.v.）或腹膜内（i.p.）给予镉（1.25 mg/kg 体重）时，胎儿对镉的吸收至少比早期研究中报道的要高 6 倍（Webb 和 Samarawickrama 1981）。静脉注射时较高剂量（1.5 和 2.0 毫克/千克体重）对母体动物是致命的，但如果腹腔注射则不会。腹腔注射的胎儿毒性然而，注射的镉随着剂量超过 1.25-2.0 毫克镉/千克体重的范围而增加。致畸反应也比之前观察到的更广泛，在静脉注射 1.25 mg Cd/kg 体重后达到最大。在 gd 10 和 i.p.虽然两种途径给药后脑积水、泌尿生殖系统异常、腭裂和其他不太常见缺陷的发生率相似，但腹膜内注射后骨骼畸形的发生率、范围和严重程度更高。比静脉注射后在 gd 12 上施用 Cd。这种反应差异不太可能用胎儿或胎盘吸收金属离子的差异来解释，因为在腹腔注射后 4 小时。给药后，胎儿 Cd 浓度与静脉注射后没有显着差异。注射后，胎盘浓度约减少 33%。这表明，静脉注射后对母体肝脏的损害更为严重。注射最佳剂量可能是另一个因素，与胎盘转运和胚胎/胎儿生物合成过程的抑制相结合，导致怀孕大鼠中镉的致畸作用。
In rats of the present (re-derived) Wistar-Porton strain that are dosed either intravenously (i.v.), or intraperitoneally (i.p.) with Cd (1.25 mg/kg body weight) on day 12 of gestation (gd 12), foetal uptake of Cd is at least 6-fold greater than that reported in an earlier study (Webb and Samarawickrama 1981). Higher doses (1.5 and 2.0 mg/kg body weight) are lethal to the maternal animal when administered i.v., but not if given ip. The foetotoxicity of i.p. injected Cd, however, increases with the dose over the range 1.25-2.0 mg Cd/kg body weight. The teratogenic response, which is also wider than that observed previously, is maximal after the injection of 1.25 mg Cd/kg body weight i.v. on gd 10 and i.p. on gd 12. Whilst the incidences of hydrocephalus, urogenital abnormalities, cleft palate and other less common defects are similar after dosing by both routes, the incidence, range and severity of skeletal malformations are greater after i.p. than after i.v. administration of Cd on gd 12. This difference in response is unlikely to be explained by a difference in either foetal, or placental uptake of the metallic ion since, at 4 h after i.p. dosing, the foetal concentration of Cd is not significantly different from that after i.v. injection, whilst the placental concentration is about 33% less. It is suggested that damage to the maternal liver, which is more severe after the i.v. injection of the optimum dose, may be an additional factor that, in conjunction with the inhibition of transport in the placenta and biosynthetic processes in the embryo/foetus, contributes to the teratogenic effects of Cd in the pregnant rat.