Reduction of caffeine teratogenicity in mice by inducing maternal drug metabolism with beta-naphthoflavone.
Reduction of caffeine teratogenicity in mice by inducing maternal drug metabolism with beta-naphthoflavone.
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通过用 β-萘黄酮诱导母体药物代谢来减少咖啡因对小鼠的致畸性。
DOI：
10.1002/tera.1420310206
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
ScottJr,WJ
中科院分区：
文献类型：
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作者：
York,RG;Randall,JL;ScottJr,WJ
在C57 BL/6 J（细胞色素P1 - 450诱导型）和AKR/J（细胞色素P1 - 450非诱导型）小鼠中研究了刺激母体药物代谢对咖啡因致畸性的影响。在妊娠第9天和第10天，以20或80 mg/kg/d剂量腹膜内（IP）给予母兽诱导剂β-萘酮（β-NF）玉米油溶液。在妊娠第11天和第12天IP给予175 mg/kg/d咖啡因去离子水溶液的致畸注射剂。在妊娠第18天处死所有母鼠，固定胎仔进行刀片切片和骨骼检查。在没有母体代谢刺激的情况下，咖啡因在两种小鼠中引起相似类型和比率的畸形。在怀孕期间用β-NF诱导药物代谢可以保护胚胎免受大量注射咖啡因的先天性毒性。胚胎死亡率、肢体畸形和血肿形成的减少在诱导型菌株中是明显的，但在不能诱导的菌株中不是。在减少畸形方面，80 mg/kg/d剂量的β-NF比20 mg/kg/d剂量的β-NF更有效，表明代谢刺激和咖啡因诱导的致畸性呈负相关。由于药物代谢增加而导致的咖啡因的快速消除伴随着毒性的降低，这表明咖啡因而不是代谢物是有毒物质。
The effect of stimulating maternal drug metabolism on caffeine teratogenicity was investigated in C57BL/6J (cytochrome P1‐450 inducible) and AKR/J (cytochrome P1‐450 noninducible) mice. The inducing agent, β‐naphthoflavone (β‐NF) in corn oil, was administered intraperiotoneally (IP) to dams at 20 or 80 mg/kg/d on days 9 and 10 of gestation. Teratogenic injections of 175 mg/kg/d caffeine in deionized water were administered IP on days 11 and 12 of gestation. All dams were sacrificed on day 18 of gestation, and fetuses were fixed for razor blade sectioning and skeletal examination. Caffeine, without maternal metabolism stimulation, caused similar types and rates of malformations in both strains of mice. Inducing drug metabolism during pregnancy with β‐NF protected the embryos from the congenital toxicities of large injections of caffeine. Reductions in embryolethality, limb malformations, and hematoma formation were evident in the inducible strain but not in the strain incapable of being induced. A dosage of eighty mg/kg/d was more effective than 20 mg/kg/d β‐NF in decreasing malformations, suggesting that stimulation of metabolism and caffeine‐induced teratogenicity are inversely related. Rapid elimination of caffeine resulting from increasing drug metabolism with the concomitant decrease in toxicity would indicate that caffeine, and not a metabolite, is the toxicant.