Developmental toxicity of dextromethorphan in zebrafish embryos/larvae

J Appl Toxicol. 2011 Mar;31(2):157-63. doi: 10.1002/jat.1576. Epub 2010 Aug 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitussive Agents / toxicity*
  • Behavior, Animal / drug effects
  • Bradycardia / chemically induced
  • Bradycardia / embryology
  • Craniofacial Abnormalities / chemically induced
  • Craniofacial Abnormalities / embryology
  • Dextromethorphan / toxicity*
  • Dose-Response Relationship, Drug
  • Edema / chemically induced
  • Edema / embryology
  • Edema, Cardiac / chemically induced
  • Edema, Cardiac / embryology
  • Embryo, Nonmammalian / drug effects*
  • Embryo, Nonmammalian / metabolism
  • Embryo, Nonmammalian / pathology
  • Embryonic Development / drug effects*
  • Feeding Behavior / drug effects
  • Gene Expression Regulation, Developmental / drug effects
  • Larva / drug effects*
  • Larva / metabolism
  • RNA, Messenger / metabolism
  • Regional Blood Flow / drug effects
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism
  • Teratogens / toxicity*
  • Yolk Sac / drug effects
  • Yolk Sac / pathology
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism


  • Antitussive Agents
  • RNA, Messenger
  • Teratogens
  • Zebrafish Proteins
  • Dextromethorphan
  • SULT3 sulfotransferase, zebrafish
  • Sulfotransferases