达丁类药物和其他处方药物的胚胎毒性,据报道对胆固醇生物合成产生非标效应
Taryn Hartley1, Hagir Abdelmagid1, Zeenat Abdulsalam2
1Department of Biological Sciences, Alabama State University, Montgomery, AL, United States; Center For NanoBiotechnology Research, Alabama State University, Montgomery, AL, United States.
Reproductive toxicology (Elmsford, N.Y.)
|December 12, 2024
概括
类药物和精神药物对胚胎发育有不同的影响. 类固醇药,早期抑制胆固醇合成,导致致死性和发育迟缓,而类固醇药,影响后期阶段,导致像小头症这样的形.
科学领域:
- 发展生物学 发展生物学
- 药理学 药理学是指药理学的学科.
- 生物化学 生物化学
背景情况:
- 胆固醇对细胞功能至关重要,不平衡与心血管和神经精神疾病等疾病有关.
- 类他类药物抑制甲基-甲基-辅酶A减少酶 (HMGCR),这是胆固醇生物合成中的关键酶.
- 在7-脱胆固醇减少酶 (DHCR7) 突变导致史密斯-莱姆利-奥皮茨综合征 (SLOS),和一些精神药物抑制DHCR7.
研究的目的:
- 研究FDA批准的他类药物和精神药物对使用Xenopus laevis的胚胎发育的影响.
- 为了比较抑制近端 (HMGCR) 与远端 (DHCR7) 胆固醇生物合成的发育毒性和表型结果.
主要方法:
- 在Xenopus laevis胚胎暴露于8种他类药物和精选的精神药物中,其度从0.1微米到50微米不等.
- 药物暴露发生在从芽细胞阶段到游泳的阶段,每天的介质变化.
- 评估了胚胎死亡率和发育表型.
主要成果:
- 类药物表现出异质的胚胎致死性;西姆瓦斯塔丁,皮塔瓦斯塔丁,洛瓦斯塔丁,塞里瓦斯塔丁和弗鲁瓦斯塔丁是最有毒的.
- 达丁类药物暴露导致发育延迟,身体轴缩短,心周胀.
- 精神药物显示出较低的胚胎死亡率,但引起了类似的发育表型,包括小头症和全脑症.
结论:
- 抑制近端胆固醇生物合成 (他类药物) 和远端胆固醇生物合成 (精神药物) 对胚胎发育具有明显但重叠的影响.
- 这些发现强调了在脊椎动物发育过程中准胆固醇生物合成途径的不同阶段的差异性影响.
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