Chiral toxicity of muscone to embryonic zebrafish heart

Ming Li; Liang Yao; Hao Chen; Xuan Ni; Yao Xu; Wengjing Dong; Mingliang Fang; Da Chen; Aowuliji; Liang Xu; Baoquan Zhao; Jiang Deng; Kevin Wh Kwok; Jingfeng Yang; Wu Dong

doi:10.1016/j.aquatox.2020.105451

Chiral toxicity of muscone to embryonic zebrafish heart

Aquat Toxicol. 2020 May:222:105451. doi: 10.1016/j.aquatox.2020.105451. Epub 2020 Feb 18.

Authors

Ming Li¹, Liang Yao², Hao Chen¹, Xuan Ni¹, Yao Xu¹, Wengjing Dong¹, Mingliang Fang³, Da Chen⁴, Aowuliji⁵, Liang Xu⁶, Baoquan Zhao⁷, Jiang Deng⁸, Kevin Wh Kwok⁹, Jingfeng Yang¹⁰, Wu Dong¹¹

Affiliations

¹ 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.
² 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.
³ School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.
⁴ School of Environment, Guangdong Key Laboratory of Environment Pollution and Health, Jinan University, Guangzhou, Guangdong 510632, China.
⁵ College of Traditional Mongolian Medicine and Pharmacy, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028000, China.
⁶ College of Chemistry and Chemical Engineering, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028000, China.
⁷ State Key Laboratory of Toxicology and Medical Countermeasures, Institute of Toxicology and Pharmacology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China.
⁸ Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi Guizhou563000, China.
⁹ Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong. Electronic address: kwh.kwok@polyu.edu.hk.
¹⁰ 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. Electronic address: yangjf@imun.edu.cn.
¹¹ 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. Electronic address: dongwu@imun.edu.cn.

PMID: 32097808
DOI: 10.1016/j.aquatox.2020.105451

Abstract

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.

Keywords: Atrial/Ventricular myosin heavy Chain; Cardiotoxicity; Chirality; Muscone; Zebrafish embryo.

MeSH terms

Animals
Cardiotoxicity
Cycloparaffins / chemistry
Cycloparaffins / toxicity*
Embryo, Nonmammalian / drug effects*
Embryonic Development / drug effects
Heart / drug effects*
Heart / embryology
Heart Rate / drug effects
Stereoisomerism
Water Pollutants, Chemical / chemistry
Water Pollutants, Chemical / toxicity*
Zebrafish / embryology

Substances

Cycloparaffins
Water Pollutants, Chemical
muscone