Chiral toxicity of muscone to embryonic zebrafish heart
Chiral toxicity of muscone to embryonic zebrafish heart
复制标题
麝香酮对斑马鱼胚胎心脏的手性毒性
DOI：
10.1016/j.aquatox.2020.105451
复制
发表时间：
2020-05-01
影响因子：
4.5
通讯作者：
Dong, Wu
中科院分区：
文献类型：
--
作者：
Li, Ming;Yao, Liang;Dong, Wu
麝香化合物经常被用来治疗心脏相关疾病，在亚洲被广泛使用。麝香酮是天然麝香最重要的生理活性化合物之一。麝香酮是一种手性化合物，又可分为S-麝香酮和R-麝香酮，两者都存在于合成麝香中。虽然这两种手性异构体在气味性质上有显著差异，但它们的毒性差异仍不清楚。本研究以斑马鱼为动物模型，比较了S麝香酮和R-麝香酮的心脏毒性。结果表明，这两种化合物对斑马鱼胚胎均有剧毒作用，导致胚胎死亡，孵化率降低，心包肿胀，心率减慢。这些毒性是通过增加MYH6和MyH7的mRNA表达，以及降低甲状腺基因(TRH、Thrβ和dio3)的表达来调节的。在相同浓度下，R-麝香酮的毒性高于S-麝香酮。为安全起见，合成麝香酮的手性异构体组成今后应谨慎调整。
Musk compounds are often used as to treat heart-related diseases and are widely used in Asia. Muscone is one of the most important physiologically active compounds of natural musk. Muscone is a chiral compound and can be further classified into S-muscone and R-muscone and both are present in synthetic musk. While these two chiral isomers have significant differences in odor properties, their difference in toxicity is still unknown. This study used zebrafish as an animal model to compare cardiac toxicities of S-muscone and R-muscone. Results showed that both compounds were acutely toxic to zebrafish embryos causing mortality, decreased hatching rate, pericardial edema, and decreased heart beat rate. These toxicities were modulated through increased Myh6 and Myh7 mRNA expression, and decreased thyroid genes (Trh, Thr beta, and Dio3) expression. R-muscone caused higher toxicity than S-muscone at the same concentration. For safety, the chiral isomer composition of synthetic muscone should be carefully regulated in the future.