首页> 外文期刊>Reproductive toxicology >Association of anxiolytic drugs diazepam and lorazepam, and the antiepileptic valproate, with heart defects--effects on cardiomyocytes in micromass (MM) and embryonic stem cell culture.
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Association of anxiolytic drugs diazepam and lorazepam, and the antiepileptic valproate, with heart defects--effects on cardiomyocytes in micromass (MM) and embryonic stem cell culture.

机译:抗焦虑药地西epa和劳拉西m以及抗癫痫药丙戊酸盐与心脏缺陷的关系-对微质量(MM)和胚胎干细胞培养中的心肌细胞的影响。

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摘要

Maternal exposure to antidepressant and antiepileptic drugs has been controversially associated with embryological malformations. The underlying mechanisms are unclear. Embryonic chick heart micromass (MM) and D3 mouse embryonic stem cell (ESC) derived cardiomyocyte cultures were treated with a series of concentrations of diazepam (DZ), lorazepam (LZ) and valproic acid (VPA). It was found that DZ and LZ significantly reduced cell beating at concentrations above and including 8 muM (P<0.05), whilst not affecting cell viability and total protein up to 50 muM in both systems, indicating teratogenic rather than cytotoxic effects. At high concentrations (>50 muM), LZ also proves to be cytotoxic in MM. Exposure of the embryonic chick heart MM cultures to 100-2000 muM VPA also showed no cytotoxic effects but the contractile activity of the cultures was significantly inhibited at those concentrations (P<0.05). These experiments provide evidence that antidepressant drugs and valproate may perturb heart development.
机译:孕妇接触抗抑郁药和抗癫痫药一直与胚胎畸形有关。潜在的机制尚不清楚。用一系列浓度的地西epa(DZ),劳拉西m(LZ)和丙戊酸(VPA)处理雏鸡心脏微质量(MM)和D3小鼠胚胎干细胞(ESC)衍生的心肌细胞培养物。发现DZ和LZ在高于和包括8μM的浓度下均能显着减少细胞跳动(P <0.05),同时在两个系统中均不影响细胞活力和总蛋白至50μM,表明具有致畸作用而不是细胞毒性作用。在高浓度(> 50μM)下,LZ在MM中也被证明具有细胞毒性。雏鸡心脏MM培养物暴露于100-2000μMVPA也没有细胞毒性作用,但在这些浓度下培养物的收缩活性受到显着抑制(P <0.05)。这些实验提供了抗抑郁药和丙戊酸盐可能扰乱心脏发育的证据。

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