Antitussive drug dextromethorphan induces developmental impairment in zebrafish

Dong-Dong Ma; Wen-Jun Shi; Zhi-Jie Lu; Jin-Ge Zhang; Li-Xin Hu; Zheng Huang; Si-Ying Li; Xiao-Bing Long; Xin Liu; Chu-Shu Huang; Guang-Guo Ying

doi:10.1016/j.jhazmat.2024.137042

Antitussive drug dextromethorphan induces developmental impairment in zebrafish

J Hazard Mater. 2024 Dec 30:486:137042. doi: 10.1016/j.jhazmat.2024.137042. Online ahead of print.

Authors

Affiliations

¹ SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China.
² SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China. Electronic address: [email protected].
³ Anti-Drug Technology Center of Guangdong Province and National Anti-Drug Laboratory Guangdong Regional Center, Guangdong Provincial Key Laboratory of Psychoactive Substances Monitoring and Safety, Guangzhou 510230, China.
⁴ SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China; School of Environment, South China Normal University, University Town, Guangzhou 510006, China; Anti-Drug Technology Center of Guangdong Province and National Anti-Drug Laboratory Guangdong Regional Center, Guangdong Provincial Key Laboratory of Psychoactive Substances Monitoring and Safety, Guangzhou 510230, China. Electronic address: [email protected].

PMID: 39742866
DOI: 10.1016/j.jhazmat.2024.137042

Abstract

Dextromethorphan (DXM) is a common ingredient in cough and cold remedies. Despite its widespread presence in aquatic environments, the impact of DXM on fish remains largely unknown. This study evaluated the developmental impairment of zebrafish embryos exposed to DXM from 2 hours post-fertilization (hpf) to 14 days post-fertilization (dpf) at five different exposure concentrations: 0.06, 0.61, 8.12, 76.3, and 827 μg/L. Results indicated a concentration-dependent increase in bioconcentration of DXM at 7 dpf and 14 dpf. The LC₅₀ at 14 dpf was 93.3 μg/L, demonstrating DXM has a high toxicity to zebrafish larvae. Additionally, DXM reduced body length and heart rate, and elevated malformation in a dose-dependent manner in larvae at 72 hpf, 7 dpf and 14 dpf. Biochemical analysis (DNA conformations and 8-hydroxy-2deoxyguanosine level) and transcriptomic analysis (DNA damage and cell cycle) indicated that DXM triggered DNA damage in larvae. Concurrently, DXM triggered DNA damage response (e.g., cell cycle arrest, DNA repair failure, and cell apoptosis) in larvae at 7 dpf and 14 dpf. These results help explain DXM caused severe developmental impairment via DNA damage-related pathways in zebrafish larvae, highlighting the importance of focusing on ecological and public health risks of DXM in natural environment.

Keywords: Apoptosis; Cell cycle arrest; DNA damage; DNA repair; Dextromethorphan.