Metal-salt potentiation of salicylate-induced teratogenesis and behavioral changes in rats.
Metal-salt potentiation of salicylate-induced teratogenesis and behavioral changes in rats.
复制标题
金属盐增强水杨酸盐诱导的大鼠致畸和行为变化。
DOI：
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发表时间：
1974
期刊：
影响因子：
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通讯作者：
H. Schumacher
中科院分区：
文献类型：
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作者：
C. Kimmel;R. Butcher;C. Vorhees;H. Schumacher
在大鼠中研究了胃肠外金属补充剂对水杨酸盐致畸性的影响。分别于妊娠第8、9、10天腹腔注射葡萄糖酸亚铁（16 mg/kg）、硫酸锰（10 mg/kg）、硫酸亚铜（6 mg/kg）或去离子水，第9天，金属盐处理后1 h，口服水杨酸钠（250或500 mg/kg）或去离子水。锰显着增强水杨酸盐的致畸作用，铁增强水杨酸盐的效果，但在较小的程度上比锰，和铜水杨酸盐致畸作用几乎没有或没有影响。水杨酸盐处理后6小时，锰和铁显着增加胚胎和母体血浆中的总水杨酸盐浓度，其中锰的作用更大。未检测到水杨酸盐对血浆蛋白结合的干扰。在第8、9和10天给予125 mg/kg阿司匹林po和16 mg/kg葡萄糖酸亚铁ip的动物的40日龄后代中研究了可能的水杨酸盐金属相互作用的产后影响。相对于溶剂对照，在阿司匹林-Fe和阿司匹林组中均观察到探索活动和平均体重增加，但迷宫学习仅在暴露于阿司匹林和Fe的动物中受损。通过肠外金属盐治疗增强水杨酸盐的产前和产后效应意味着母体循环中的水杨酸盐-金属相互作用，并表明螯合作用是水杨酸盐致畸作用的一种机制。
The effects of parenteral metal supplements on salicylate teratogenicity were studied in rats. Ferrous gluconate (16 mg/kg), manganous sulfate (10 mg/kg), cuprous sulfate (6 mg/kg), or deionized water were given ip on days 8, 9, and 10 of gestation, Sodium salicylate (250 or 500 mg/kg) or deionized water was administered po on day 9, l h after the metal-salt treatment. Mn significantly enhanced the teratogenic effects of salicylate, Fe potentiated the salicylate effect but to a lesser extent than Mn, and Cu had little or no effect on salicylate teratogenicity. Mn and Fe significantly increased total salicylate concentration in both embryos and maternal plasma at 6 h after salicylate treatment, with Mn having the greater effect. No interference with plasma-protem binding of salicylate could be detected. Posrnatal effects of possible salicylatemetal interactions were studied in 40-day-old offspring of animals treated with 125 mg/kg aspirin po and 16 mg/kg ferrous gluconate ip on days 8, 9, and 10. Increased exploratory activity and mean body weight were observed in both the aspirin-Fe and aspirin groups relative to vehicle controls, but maze learning was impaired only in animals exposed to both aspirin and Fe. The potentiation of the pre- and postnatal effects of salicylate by parenteral metal-salt treatment implies a salicylate-metal interaction in the maternal circulation and suggests chelation as a mechanism of the teratogenic action of salicylate.