Tolbutamide: placental transfer, tissue distribution, and metabolic effects in murine embryos.
Tolbutamide: placental transfer, tissue distribution, and metabolic effects in murine embryos.
复制标题
甲苯磺丁脲：胎盘移植、组织分布和对小鼠胚胎的代谢影响。
DOI：
10.1111/j.1600-0773.1998.tb01426.x
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Emanuel,AN
中科院分区：
文献类型：
--
作者：
Smoak,IW;Emanuel,AN
甲苯磺脲是一种口服降糖药，在人体上有可疑的致畸作用，在实验动物中有致畸作用，但其潜在作用机制尚不清楚。本研究检测了母体给药后9.5天和10.5天的母胎-胎鼠甲苯磺丁胺的转运，以及孕期10.5天胚胎头部、心脏和躯干部位的药物浓度。妊娠8.5天的胚胎暴露于体外培养的甲苯磺丁胺中，在6、12和24小时后检测葡萄糖的摄取、糖酵解和蛋白质含量。甲苯丁胺从母体血清到胚外液的转移呈剂量依赖关系，在妊娠9.5天和10.5天，胚胎心脏中的甲苯丁胺水平在妊娠10.5天达到最高水平。在妊娠8.5天，甲苯丁胺暴露使6小时糖酵解减少，24小时糖酵解增加。在6、12或24小时对葡萄糖摄取没有影响。胚胎蛋白质含量反映了甲苯丁胺暴露24小时后的生长迟缓。因此，在妊娠9.5天和10.5天母亲给药后，小鼠胚胎直接暴露于甲苯丁胺，药物浓度在胚胎心脏内。在整个胚胎中，甲苯丁胺引起的葡萄糖代谢的变化不如在成人组织中报道的那么明显。
Tolbutamide is a sulfonylurea oral hypoglycaemic agent with suspected teratogenicity in humans and demonstrated teratogenicity in laboratory animals, but the underlying mechanism is unknown. This study examined maternalto–conceptus tolbutamide transfer on gestational days 9.5 and 10.5 and drug concentration in embryonic head, heart, and trunk regions on gestational day 10.5 after maternal dosing in mouse. Embryos exposed to tolbutamidein vitroon gestational day 8.5 were assayed for glucose uptake, glycolysis, and protein content after 6, 12, and 24 hr. Dose–dependent tolbutamide transfer from maternal serum to extraembryonic fluid occurred on gestational day 9.5 and 10.5, with highest tolbutamide levels in embryonic heart on gestational day 10.5.In vitrotolbutamide exposure on gestational day 8.5 decreased glycolysis at 6 hr, increased glycolysis at 24 hr. and had no effect on glucose uptake at 6, 12, or 24 hr. Embryonic protein content reflected growth retardation after 24 hr tolbutamide exposure. Thus, mouse embryos are directly exposed to tolbutamide after maternal dosing on gestational day 9.5 and 10.5, with concentration of drug within embryonic heart. Tolbutamide–induced changes in glucose metabolism are less apparent in whole embryos than reported in adult tissues.