Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicant and Toxicology, Collage of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China.
Inner Mongolia Key Laboratory of Toxicant Monitoring and Toxicant and Toxicology, Collage of Animal Science and Technology, Inner Mongolia University for Nationalities, Tongliao, Inner Mongolia 028000, China; National Demonstration Center for Experimental Fisheries Science Education, Shanghai Ocean University, Shanghai 201306, China; Function Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture, Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao 266071, China.
Aquat Toxicol. 2020 May;222:105451. doi: 10.1016/j.aquatox.2020.105451. Epub 2020 Feb 18.
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, Thrβ, 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.
麝香化合物常用于治疗与心脏相关的疾病，在亚洲被广泛应用。麝香酮是天然麝香中最重要的具有生理活性的化合物之一。麝香酮是一种手性化合物，可进一步分为 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特性上有显著差异，但它们的毒性差异尚不清楚。本研究使用斑马鱼作为动物模型，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具有急性毒性，导致死亡率增加、孵化率降低、心包水肿和心率降低。这些毒性是通过增加 Myh6 和 Myh7 mRNA 的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。为了安全起见，未来应仔细调节合成麝香中手性异构体的组成。
