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一项关于使用载体向啮齿动物全胚胎培养物中添加非水溶性化合物的研究。

A study of vehicles for dosing rodent whole embryo culture with non aqueous soluble compounds.

作者信息

Augustine-Rauch Karen A, Zhang Qin, Kleinman Mark, Lawton Richard, Welsh Michael J

机构信息

Department of Reproductive Toxicology, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA.

出版信息

Reprod Toxicol. 2004 May;18(3):391-8. doi: 10.1016/j.reprotox.2004.01.006.

Abstract

In rodent whole embryo culture (WEC), finding vehicles for non-aqueous-soluble compounds has been problematic due to developmental toxicity associated with many solvents. The purpose of this study was to identify alternative vehicles for insoluble compounds. In WEC, we evaluated carrier solutions containing bovine serum albumin (BSA) and glycerol as well as the solvents, formamide, dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and ethanol, for relative teratogenicity and delivery of the insoluble teratogen, all-trans retinoic acid (RA). At a concentration of <or=0.04%, formamide and DMF exhibited no significant toxicity to cultured rat embryos and were effective at delivering RA to the embryo. The BSA and glycerol carrier solutions were not teratogenic, although both inhibited robust formation of yolk sac vasculature. Both solutions delivered RA to the cultured rat embryos at higher doses. In summary, all four solvents/solutions may have utility as vehicles dependent upon the chemical properties of the compound to be solubilized.

摘要

在啮齿动物全胚胎培养(WEC)中,由于许多溶剂具有发育毒性,为非水溶性化合物寻找载体一直存在问题。本研究的目的是确定不溶性化合物的替代载体。在WEC中,我们评估了含有牛血清白蛋白(BSA)和甘油的载体溶液以及溶剂甲酰胺、二甲基甲酰胺(DMF)、二甲基亚砜(DMSO)和乙醇对相对致畸性和不溶性致畸剂全反式维甲酸(RA)传递的影响。在浓度≤0.04%时,甲酰胺和DMF对培养的大鼠胚胎无明显毒性,且能有效地将RA传递给胚胎。BSA和甘油载体溶液没有致畸性,尽管两者都抑制了卵黄囊血管的强劲形成。两种溶液都能以更高剂量将RA传递给培养的大鼠胚胎。总之,根据待溶解化合物的化学性质,所有四种溶剂/溶液都可能用作载体。

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