水性阿托瓦斯塔丁的环境相关度会导致Xenopus laevis胆固醇生物合成和基因表达模式的改变
1Department of Coastal Sciences, University of Southern Mississippi, Hattiesburg, MS 39407, USA.
Aquatic toxicology (Amsterdam, Netherlands)
|February 24, 2024
概括
对阿托瓦斯塔丁 (一种他类药物) 的环境暴露可以扰乱成长中的青 (Xenopus laevis) 的类固醇生产. 这项研究表明,低度会改变胆固醇生物合成和基因表达,影响两动物的发育.
科学领域:
- 环境毒理学环境毒理学
- 内分泌学 在内分泌学.
- 两动物发育生物学
背景情况:
- 药物化合物,包括像阿托瓦斯塔丁这样的他类药物,在水生环境中经常被检测到.
- 暴露于阿托瓦斯塔丁可能会对水生生物构成风险,特别是在类固醇生成方面.
- 两动物模型Xenopus laevis是一个适合研究环境污染物对发育的影响的生物.
研究的目的:
- 调查假设慢性暴露于低度的阿托瓦斯塔丁会对Xenopus laevis的类固醇生产产生不利影响.
- 评估阿托瓦斯塔丁对胆固醇生物合成和类固醇生成途径的影响.
- 评估环境相关的阿托瓦斯塔丁度对Xenopus laevis不同生命阶段的影响.
主要方法:
- 青胚胎发育试验 (FETAX) 评估发育毒性和降低胆固醇.
- 变形试验和慢性流通暴露,以评估60天内对和成人的影响.
- RNA测序 (RNAseq) 和定量聚合酶链反应 (qPCR) 用于分析基因表达变化.
主要成果:
- 阿托瓦斯塔丁暴露显著改变了变形的胆固醇生物合成.
- 剂量依赖的cyp19a1表达的增加表明受影响的类固醇生成途径.
- RNAseq揭示了全球转录特征的显著变化,与失调的胆固醇生物合成相一致.
- 在成年人中,qPCR显示特定基因 (男性hmgcr,女性cyp3a4) 的下调.
结论:
- 长期暴露于环境相关度的阿托瓦斯塔丁可以影响两动物的早期生命阶段.
- 阿托尔瓦斯塔丁不调节关键的分子通路,包括胆固醇生物合成和类固醇生成.
- 这些发现强调了制药污染在水生生态系统中的潜在生态风险.
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