Developmental toxicity of dextromethorphan in zebrafish embryos/larvae

✍ Scribed by Zheng Xu; Frederick E. Williams; Ming-Cheh Liu

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 450 KB
• Volume: 31
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.1576

✦ Synopsis

Abstract

Dextromethorphan is widely used in over‐the‐counter cough and cold medications. Its efficacy and safety for infants and young children remains to be clarified. The present study was designed to use zebrafish as a model to investigate the potential toxicity of dextromethorphan during embryonic and larval development. Three sets of zebrafish embryos/larvae were exposed to dextromethorphan at 24, 48 and 72 h post fertilization (hpf), respectively, during the embryonic/larval development. Compared with the 48 and 72 hpf exposure sets, the embryos/larvae in the 24 hpf exposure set showed much higher mortality rates which increased in a dose‐dependent manner. Bradycardia and reduced blood flow were observed for the embryos/larvae treated with increasing concentrations of dextromethorphan. Morphological effects of dextromethorphan exposure, including yolk sac and cardiac edema, craniofacial malformation, lordosis, non‐inflated swim bladder and missing gill, were also more frequent and severe among zebrafish embryos/larvae exposed to dextromethorphan at 24 hpf. Whether the more frequent and severe developmental toxicity of dextromethorphan observed among the embryos/larvae in the 24 hpf exposure set, as compared with the 48 and 72 hpf exposure sets, is due to the developmental expression of the phase I and phase II enzymes involved in the metabolism of dextromethorphan remains to be clarified. A reverse transcription‐polymerase chain reaction analysis, nevertheless, revealed developmental stage‐dependent expression of mRNAs encoding SULT3 ST1 and SULT3 ST3, two enzymes previously shown to be capable of sulfating dextrorphan, an active metabolite of dextromethorphan. Copyright © 2010 John Wiley & Sons, Ltd.