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. 2003 Dec;111(16):1920–1925. doi: 10.1289/ehp.6386

The type B brevetoxin (PbTx-3) adversely affects development, cardiovascular function, and survival in Medaka (Oryzias latipes) embryos.

Jamie R Colman 1, John S Ramsdell 1
PMCID: PMC1241767  PMID: 14644667

Abstract

Brevetoxins are produced by the red tide dinoflagellate Karenia brevis. The toxins are lipophilic polyether toxins that elicit a myriad of effects depending on the route of exposure and the target organism. Brevetoxins are therefore broadly toxic to marine and estuarine animals. By mimicking the maternal route of exposure to the oocytes in finfish, we characterized the adverse effects of the type B brevetoxin brevetoxin-3 (PbTx-3) on embryonic fish development and survival. The Japanese rice fish, medaka (Oryzias latipes), was used as the experimental model in which individual eggs were exposed via microinjection to various known concentrations of PbTx-3 dissolved in an oil vehicle. Embryos injected with doses exceeding 1.0 ng/egg displayed tachycardia, hyperkinetic twitches in the form of sustained convulsions, spinal curvature, clumping of the erythrocytes, and decreased hatching success. Furthermore, fish dosed with toxin were often unable to hatch in the classic tail-first fashion and emerged head first, which resulted in partial hatches and death. We determined that the LD(50) (dose that is lethal to 50% of the fish) for an injected dose of PbTx-3 is 4.0 ng/egg. The results of this study complement previous studies of the developmental toxicity of the type A brevetoxin brevetoxin-1 (PbTx-1), by illustrating in vivo the differing affinities of the two congeners for cardiac sodium channels. Consequently, we observed differing cardiovascular responses in the embryos, wherein embryos exposed to PbTx-3 exhibited persistent tachycardia, whereas embryos exposed to PbTx-1 displayed bradycardia, the onset of which was delayed.

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Selected References

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  1. Bigbee J. W., Sharma K. V., Gupta J. J., Dupree J. L. Morphogenic role for acetylcholinesterase in axonal outgrowth during neural development. Environ Health Perspect. 1999 Feb;107 (Suppl 1):81–87. doi: 10.1289/ehp.99107s181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borison H. L., McCarthy L. E., Ellis S. Neurological analysis of respiratory, cardiovascular and neuromuscular effects of brevetoxin in cats. Toxicon. 1985;23(3):517–524. doi: 10.1016/0041-0101(85)90036-4. [DOI] [PubMed] [Google Scholar]
  3. Bottein Dechraoui Marie-Yasmine, Ramsdell John S. Type B brevetoxins show tissue selectivity for voltage-gated sodium channels: comparison of brain, skeletal muscle and cardiac sodium channels. Toxicon. 2003 Jun;41(7):919–927. doi: 10.1016/s0041-0101(03)00088-6. [DOI] [PubMed] [Google Scholar]
  4. Brimijoin S., Koenigsberger C. Cholinesterases in neural development: new findings and toxicologic implications. Environ Health Perspect. 1999 Feb;107 (Suppl 1):59–64. doi: 10.1289/ehp.99107s159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Catterall W. A. Cellular and molecular biology of voltage-gated sodium channels. Physiol Rev. 1992 Oct;72(4 Suppl):S15–S48. doi: 10.1152/physrev.1992.72.suppl_4.S15. [DOI] [PubMed] [Google Scholar]
  6. Catterall W. A., Risk M. Toxin T4(6) from Ptychodiscus brevis (formerly Gymnodinium breve) enhances activation of voltage-sensitive sodium channels by veratridine. Mol Pharmacol. 1981 Mar;19(2):345–348. [PubMed] [Google Scholar]
  7. Dickey R., Jester E., Granade R., Mowdy D., Moncreiff C., Rebarchik D., Robl M., Musser S., Poli M. Monitoring brevetoxins during a Gymnodinium breve red tide: comparison of sodium channel specific cytotoxicity assay and mouse bioassay for determination of neurotoxic shellfish toxins in shellfish extracts. Nat Toxins. 1999;7(4):157–165. doi: 10.1002/(sici)1522-7189(199907/08)7:4<157::aid-nt52>3.0.co;2-#. [DOI] [PubMed] [Google Scholar]
  8. Edmunds J. S., McCarthy R. A., Ramsdell J. S. Ciguatoxin reduces larval survivability in finfish. Toxicon. 1999 Dec;37(12):1827–1832. doi: 10.1016/s0041-0101(99)00119-1. [DOI] [PubMed] [Google Scholar]
  9. Johnson G. L., Spikes J. J., Ellis S. Cardiovascular effects of brevetoxins in dogs. Toxicon. 1985;23(3):505–515. doi: 10.1016/0041-0101(85)90035-2. [DOI] [PubMed] [Google Scholar]
  10. Kimm-Brinson K. L., Ramsdell J. S. The red tide toxin, brevetoxin, induces embryo toxicity and developmental abnormalities. Environ Health Perspect. 2001 Apr;109(4):377–381. doi: 10.1289/ehp.01109377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Morohashi A., Satake M., Naoki H., Kaspar H. F., Oshima Y., Yasumoto T. Brevetoxin B4 isolated from greenshell mussels Perna canaliculus, the major toxin involved in neurotoxic shellfish poisoning in New Zealand. Nat Toxins. 1999;7(2):45–48. doi: 10.1002/(sici)1522-7189(199903/04)7:2<45::aid-nt34>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  12. Plakas Steven M., el-Said Kathleen R., Jester Edward L. E., Granade H. Ray, Musser Steven M., Dickey Robert W. Confirmation of brevetoxin metabolism in the Eastern oyster (Crassostrea virginica) by controlled exposures to pure toxins and to Karenia brevis cultures. Toxicon. 2002 Jun;40(6):721–729. doi: 10.1016/s0041-0101(01)00267-7. [DOI] [PubMed] [Google Scholar]
  13. Poli M. A., Mende T. J., Baden D. G. Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes. Mol Pharmacol. 1986 Aug;30(2):129–135. [PubMed] [Google Scholar]
  14. Poli M. A., Musser S. M., Dickey R. W., Eilers P. P., Hall S. Neurotoxic shellfish poisoning and brevetoxin metabolites: a case study from Florida. Toxicon. 2000 Jul;38(7):981–993. doi: 10.1016/s0041-0101(99)00191-9. [DOI] [PubMed] [Google Scholar]
  15. Renaud J. F., Romey G., Lombet A., Lazdunski M. Developmental properties of the fast Na+ channel in embryonic cardiac cells using neurotoxins. Toxicon. 1982;20(1):17–25. doi: 10.1016/0041-0101(82)90139-8. [DOI] [PubMed] [Google Scholar]
  16. Templeton C. B., Poli M. A., LeClaire R. D. Cardiorespiratory effects of brevetoxin (PbTx-2) in conscious, tethered rats. Toxicon. 1989;27(9):1043–1049. doi: 10.1016/0041-0101(89)90155-4. [DOI] [PubMed] [Google Scholar]
  17. Washburn B. S., Baden D. G., Gassman N. J., Walsh P. J. Brevetoxin: tissue distribution and effect on cytochrome P450 enzymes in fish. Toxicon. 1994 Jul;32(7):799–805. doi: 10.1016/0041-0101(94)90005-1. [DOI] [PubMed] [Google Scholar]

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