THE HONEYBEE SYNDROME - IMPLICATIONS OF THE TERATOGENICITY OF MANNOSE IN RAT-EMBRYO CULTURE
THE HONEYBEE SYNDROME - IMPLICATIONS OF THE TERATOGENICITY OF MANNOSE IN RAT-EMBRYO CULTURE
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DOI：
10.1056/nejm198401263100404
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发表时间：
1984-01-01
影响因子：
158.5
通讯作者：
GORMAN, L
中科院分区：
文献类型：
--
作者：
FREINKEL, N;LEWIS, NJ;GORMAN, L
人们认识到D-甘露糖对蜜蜂的致死作用已有50多年的历史。D-甘露糖的另一种毒性作用是在大鼠胚胎的培养过程中，从早期的头折叠阶段到26-29天的体节阶段(妊娠9.5-11.5天)。在培养液中添加1.5 mg/ml的D-甘露糖可导致约2/3的胚胎生长迟缓和神经管闭合错误。甘露糖效应发生在培养的前24小时，并伴随着对糖酵解的适度抑制，糖酵解构成了这一发育阶段的主要能量途径。添加更多的葡萄糖以保持糖酵解通量或增加大气中的氧气以促进氧化代谢抵消了甘露糖的致畸作用。新陈代谢的脆弱性存在于器官发生的早期，在氧化灵活性建立之前。这些发现可以作为一个模型来解释许多其他看似无关的药物的致畸性，这些药物可能在这个脆弱的阶段通过扰乱糖酵解来发挥作用。
Lethal effects of D-mannose in the honeybee have been recognized for more than 50 yr. Another toxic effect of D-mannose was observed during culture of rat embryos from the early head-fold stage to the 26-29-somite stage (days 9.5-11.5 of gestation). Addition to culture mediums of 1.5 mg of D-mannose/ml caused growth retardation and faulty neural-tube closure in approximately 2/3 of the embryos. Mannose effects occurred during the first 24 h of culture and were attended by modest inhibition of the glycolysis that constitutes the principal energy pathway at this stage of development. Adding more glucose to preserve glycolytic flux or increasing atmospheric O2 to promote oxidative metabolism offset the mannose teratogenesis. Metabolic vulnerabilities exist during early organogenesis, before oxidative flexibility is established. Findings may serve as a model to explain the teratogenicity of many other seemingly unrelated agents that could act by perturbing glycolysis at this vulnerable stage.