Developmental toxicity of domoic acid in zebrafish (Danio rerio).
Domoic acid (DA) is a rigid analog of the excitatory amino acid glutamate. It is produced by the diatom genus Pseudo-nitzschia and is a potent neurotoxin in both adult and developing animals. We have used zebrafish (Danio rerio) as a model to investigate and characterize the developmental toxicity of DA. Domoic acid was administered by microinjection to fertilized eggs at the 128- to 512-cell stages in concentrations ranging from 0.12 to 17 mg/kg (DA/egg weight). DA reduced hatching success by 40% at 0.4 mg/kg and by more than 50% at doses of 1.2 mg/kg and higher. Fifty percent of embryos treated with 1.2 mg/kg DA showed marked tonic-clonic type convulsions at 2 days post fertilization. Four days post fertilization (dpf), all embryos treated with 4.0 mg/kg DA and higher showed a complete absence of touch response reflexes. Commencing 5 dpf, rapid and constant pectoral fin movements were observed, a response which may be related to the hallmark effect in rodents of stereotypic scratching. These data indicate that zebrafish show symptoms of developmental DA toxicity as well as a similar sensitivity comparable to the effects of DA characterized in laboratory rodents.
Tiedeken
Jessica A
JA
Marine Biotoxins Program, Center for Coastal Environmental Health and Biomolecular Research, NOAA, National Ocean Service, 219 Fort Johnson Rd., Charleston, SC 29412, USA.
Ramsdell
John S
JS
Ramsdell
Ann F
AF
D000014:Abnormalities, Drug-Induced / Q000473:pathology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005260:Female; D007608:Kainic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D008297:Male; D008845:Microinjections; D009498:Neurotoxins / Q000633:toxicity*; D012018:Reflex / Q000187:drug effects; D013550:Swimming; D015027:Zebrafish / Q000254:growth & development*
D009498:Neurotoxins; C012301:domoic acid; D007608:Kainic Acid