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Updated: Jun 4, 2025
Small Molecule Screening and Toxicity Testing in Early-stage Zebrafish Larvae
Published on: March 7, 2025
Antitussive drug dextromethorphan induces developmental impairment in zebrafish
Dong-Dong Ma1, Wen-Jun Shi1, Zhi-Jie Lu1
1SCNU 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.
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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.
