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Sub-lethal Camphor Exposure Triggers Oxidative Stress, Cardiotoxicity, and Cardiac Physiology Alterations in Zebrafish Embryos

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Abstract

Camphor is a terpene ketone with aromatic and volatile properties in nature derived from the bark of Cinnamomum camphora or synthesized from turpentine. Camphor exhibits various biological properties such as anti-microbial, anti-viral, anti-coccidial, and anti-cancer. It is also used as a form of topical medication for skin irritation, joint pain, and as a relief for itching from insect bites. However, even though the high dose of camphor has been documented to be toxic/lethal in humans in different studies, camphor’s developmental toxicity has not yet been explored, and its extensive mechanism of action is still unclear. In the present study, we aimed to assess the toxic effects of camphor in zebrafish embryos in the initial developmental stages. The obtained results demonstrated that a sub-lethal dose of camphor caused a decrease in hatching rate, body length, and substantial elevation in malformation rate on zebrafish embryos. On further observation, in the following time frame, curved body and pericardial edema of zebrafish were also observed. Furthermore, exposure to a sub-lethal dose of camphor was also able to trigger cardiotoxicity in zebrafish larvae. Later, on subsequent biochemical analysis, it was found that the antioxidant capacity inhibition and oxidative stress elevation that occurred after camphor exposure might be associated with the inhibition of total superoxide dismutase (SOD) activity and an increase in reactive oxygen species (ROS) and malondialdehyde (MDA) concentration. In addition, compared to the control group, several apoptotic cells in treated zebrafish were also found to be elevated. Finally, after further investigation on marker gene expressions, we conclude that the developmental toxicity of camphor exposure might be associated with apoptosis elevation and oxidative stress. Taken together, the current study provides a better understanding of the developmental toxicity of camphor on zebrafish, a promising alternative animal model to assess the developmental toxicity of chemical compounds.

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Acknowledgements

This study was funded from the Project of Guangxi Innovation-Driven Development with Grant Number AA17202040-2; the Project of Guangxi Key-Research Development with Grant Number AB17292050; the Project of GXTCMHYYJY Science and Technology with Grant Number 2018ZD005-C01; and the Project of Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica with Grant Number (19-050-39-A4; 19-245-1-A3; 20-065-38-A1/A3); Development Program of High-level Talent Team under Qihuang Project of Guangxi University of Chinese Medicine (2018006).

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Correspondence to Chung-Der Hsiao, Er-Wei Hao, Xiao-Tao Hou or Jia-Gang Deng.

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The authors declare no conflicts of interest. The funders had no role in the study’s design; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Du, ZC., Xia, ZS., Zhang, MZ. et al. Sub-lethal Camphor Exposure Triggers Oxidative Stress, Cardiotoxicity, and Cardiac Physiology Alterations in Zebrafish Embryos. Cardiovasc Toxicol 21, 901–913 (2021). https://doi.org/10.1007/s12012-021-09682-x

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