PUBLICATION
Developmental toxicity of dextromethorphan in zebrafish embryos/larvae
- Authors
- Xu, Z., Williams, F.E., and Liu, M.C.
- ID
- ZDB-PUB-100826-23
- Date
- 2011
- Source
- Journal of applied toxicology : JAT 31(2): 157-163 (Journal)
- Registered Authors
- Williams, Fred
- Keywords
- dextromethorphan, developmental toxicity, cytosolic sulfotransferase, SULT, zebrafish
- 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
- PubMed
- 20737414 Full text @ J. Appl. Toxicol.
- CTD
- 20737414
Citation
Xu, Z., Williams, F.E., and Liu, M.C. (2011) Developmental toxicity of dextromethorphan in zebrafish embryos/larvae. Journal of applied toxicology : JAT. 31(2):157-163.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping