Skip to main content
SpringerLink
Log in

Brevetoxins: Toxicological Profile

  • Reference work entry
  • First Online:
Marine and Freshwater Toxins

Part of the book series: Toxinology ((TOXI))

Abstract

Brevetoxins (PbTxs) are polyether ladder-shaped neurotoxins produced by the dinoflagellate Karenia brevis. Blooms of K. brevis have been recorded since the mid-1800s, principally in the Gulf of Mexico but occasionally along the mid and south Atlantic coasts. Blooms may be accompanied by public health issues as well as significant mortalities of marine mammals, such as bottlenose dolphins and manatees, fishes, sea birds, and sea turtles. PbTxs bind to the voltage-gated sodium channels (VGSCs), leading to persistent activation of neuronal, muscle, and cardiac cells. In humans, after consumption of contaminated shellfish (oysters, clams, whelks), these toxins cause a syndrome known as neurotoxic shellfish poisoning (NSP), characterized by nausea, diarrhea, vomiting, abdominal pain, paresthesia, myalgia, ataxia, bradycardia, loss of coordination, vertigo, and mydriasis. The ingestion of contaminated seafood represents the most dangerous route of exposure for humans. However, when PbTxs are aerosolized through the disruption of K. brevis cells by breaking waves or winds, people can suffer from respiratory effects such as conjunctivitis, rhinorrhea, and bronchoconstriction. Due to successful shellfish monitoring programs managed by the Gulf coast states, cases of human intoxications are fortunately rather rare, and no human fatalities have been attributed to NSP.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 299.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Baden DG, Bourdelais AJ, Jacocks H, Michelliza S, Naar J. Natural and derivative brevetoxins: historical background, multiplicity, and effects. Environ Health Perspect. 2005;113(5):621–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benson J, Hahn F, March T, McDonald J, Sopori M, Seagrave J, Gomez A, Bourdelais A, Naar J, Zaias J, Bossart G, Baden D. Inhalation of brevetoxin 3 in rats exposed for 5 days. J Toxicol Environ Health A. 2004;67:1443–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benson JM, Hahn FF, March TH, McDonald JD, Gomez AP, Sopori MJ, Boudelais AJ, Naar J, Zaias J, Bossart GD, Baden DG. Inhalation toxicity of brevetoxin 3 in rats exposed for twenty-two days. Environ Health Perspect. 2005;113:626–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bossart GD, Baden DG, Ewing RY, Roberts B, Wright SD. Brevetoxicosis in manatees (Trichechus manatus latirostris) from the 1996 epizootic: gross, histologic, and immunohistochemical features. Toxicol Pathol. 1998;26(2):276–82.

    Article  CAS  PubMed  Google Scholar 

  • Brand E, Campbell L, Bresnan E. Karenia: the biology and ecology of a toxic genus. Harmful Algae. 2012;14:156–78.

    Article  Google Scholar 

  • Dechraoui MY, Wang Z, Ramsdell JS. Intrinsic potency of synthetically prepared brevetoxin cysteine metabolites BTX-B2 and desoxyBTX-B2. Toxicon. 2007;50(6):825–34.

    Article  CAS  PubMed  Google Scholar 

  • Feinstein A, Ceurvels AR, Hutton RF, Snoek E. Red tide outbreaks off the Florida west coast. Coral Gables: The Marine Laboratory, University of Miami; 1955. pp. 55–15

    Google Scholar 

  • Flewelling LJ, Naar JP, Abbott JP, Baden DG, Barros NB, Bossart GD, et al. Brevetoxicosis: red tides and marine mammal mortalities. Nature. 2005;435(7043):755–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gawley RE, Rein KS, Jeglitsch G, Adams DJ, Theodorakis EA, Tiebes J, Nicolaou KC, Baden DG. The relationship of brevetoxin ‘length’ and A-ring functionality to binding and activity in neuronal sodium channels. Chem Biol. 1995;2(8):533–41.

    Article  CAS  PubMed  Google Scholar 

  • Hoagland P, Jin D, Beet A, Kirkpatrick B, Reich A, Ullmann S, Fleming LE, Kirkpatrick G. The human health effects of Florida red tide (FRT) blooms: an expanded analysis. Environ Int. 2014;68:144–53.

    Article  CAS  PubMed  Google Scholar 

  • Isbister GK, Kiernan MC. Neurotoxic marine poisoning. Lancet Neurol. 2005;4:218–28.

    Article  Google Scholar 

  • Kemppainen BW, Reifenrath WG, Stafford RG, Mehta M. Methods for in vitro skin absorption studies of a lipophilic toxin produced by red tide. Toxicology. 1991;66(1):1–17.

    Article  CAS  PubMed  Google Scholar 

  • Kirkpatrick B, Fleming LE, Squicciarini D, Backer LC, Clark R, Abraham W, Benson J, Cheng YS, Johnson D, Pierce R, Zaias J, Bossart GD, Baden DG. Literature review of Florida red tide: implications for human health effects. Harmful Algae. 2004;3(2):99–115.

    Article  PubMed  PubMed Central  Google Scholar 

  • Landsberg JH. The effects of harmful algal blooms on aquatic organisms. Rev Fish Sci. 2002;10:113–390.

    Article  Google Scholar 

  • Landsberg JH, Flewelling LJ, Naar J. Karenia brevis red tides, brevetoxins in the food web, and impacts on natural resources: decadel advancements. Harmful Algae. 2009;8:598–607.

    Article  CAS  Google Scholar 

  • Leighfield TA, Muha N, Ramsdell JS. Brevetoxin B is a clastogen in rats, but lacks mutagenic potential in the SP-98/100 Ames test. Toxicon. 2009;54(6):851–6.

    Article  CAS  PubMed  Google Scholar 

  • Leighfield TA, Muha N, Ramsdell JS. Tissue distribution of amino acid- and lipid-brevetoxins after intravenous administration to C57BL/6 mice. Chem Res Toxicol. 2014;27(7):1166–75.

    Article  CAS  PubMed  Google Scholar 

  • Lin YY, Risk M. Isolation and structure of brevetoxin B from the “red tide” dinoflagellate Ptychodiscus brevis (Gymnodinium breve). J Am Chem Soc. 1981;103:6773–5.

    Article  CAS  Google Scholar 

  • Morris PD, Campbell DS, Taylor TJ, Freeman JI. Clinical and epidemiological features of neurotoxic shellfish poisoning in North Carolina. Am J Public Health. 1991;81(4):471–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murrell RN, Gibson JE. Brevetoxins 2, 3, 6, and 9 show variability in potency and cause significant induction of DNA damage and apoptosis in Jurkat E6-1 cells. Arch Toxicol. 2009;83(11):1009–19.

    Article  CAS  PubMed  Google Scholar 

  • Plakas SM, Dickey RW. Advances in monitoring and toxicity assessment of brevetoxins in molluscan shellfish. Toxicon. 2010;56(2):137–49.

    Article  CAS  PubMed  Google Scholar 

  • Poli MA. Brevetoxins: pharmacology, toxicokinetics and detection. In: Fingerman M, Nagabhushanam R, editors. Recent advances in marine biothecnology. volume 7: seafood safety and human health, Chap 1. Enfield: Science Publisher; 2002.

    Google Scholar 

  • Poli MA, Mende TJ, Baden DG. Brevetoxins, unique activators of voltage-sensitive sodium channels, bind to specific sites in rat brain synaptosomes. Mol Pharmacol. 1986;30(2):129–35.

    CAS  PubMed  Google Scholar 

  • Poli MA, Templeton CB, Thompson WL, Hewetson JF. Distribution and elimination of brevetoxin PbTx-3 in rats. Toxicon. 1990;28(8):903–10.

    Article  CAS  PubMed  Google Scholar 

  • Poli MA, Musser SM, Dickey RW, Eilers PP, Hall S. Neurotoxic shellfish poisoning and brevetoxin metabolites: a case study from Florida. Toxicon. 2000;38(7):981–93.

    Article  CAS  PubMed  Google Scholar 

  • Purkerson-Parker SL, Fieber LA, Rein KS, Podona T, Baden DG. Brevetoxin derivatives that inhibit toxin activity. Chem Biol. 2000;7(6):385–93.

    Article  CAS  PubMed  Google Scholar 

  • Ramsdell JS. The molecular and integrative basis to brevetoxin toxicity. In: Botana LM, editor. Seafood and freshwater toxins: pharmacology, physiology, and detection. 2nd ed. Boca Raton: CRC Press; 2008.

    Google Scholar 

  • Rein KS, Baden DG, Gawley RE. Conformational analysis of the sodium channel modulator, brevetoxin A, comparison with brevetoxin B conformations, and a hypothesis about the common pharmacophore of the “site 5” toxins. J Org Chem. 1994a;59(8):2101–6.

    Article  CAS  Google Scholar 

  • Rein KS, Lynn B, Gawley RE, Baden DG, Brevetoxin B. Chemical modifications, synaptosome binding, toxicity, and an unexpected conformational effect. J Org Chem. 1994b;59:2107–13.

    Article  CAS  Google Scholar 

  • Shen M, Xu J, Tsang TY, Au DW. Toxicity comparison between Chattonella marina and Karenia brevis using marine medaka (Oryzias melastigma): evidence against the suspected ichthyotoxins of Chattonella marina. Chemosphere. 2010;80(5):585–91.

    Article  CAS  PubMed  Google Scholar 

  • Shimizu Y, Chou HN, Bando H, Van Duyne G, Clardy J. Structure of brevetoxin A (GB-1 toxin), the most potent toxin in the Florida red tide organism Gymnodinium breve (Ptychodiscus brevis). J Am Chem Soc. 1986;108(3):514–5.

    Article  CAS  PubMed  Google Scholar 

  • Tian L, Wang M, Li X, Lam PK, Wang M, Wang D, Chou HN, Li Y, Chan LL. Proteomic modification in gills and brains of medaka fish (Oryzias melastigma) after exposure to a sodium channel activator neurotoxin, brevetoxin-1. Aquat Toxicol. 2011;104(3–4):211–7.

    Article  CAS  PubMed  Google Scholar 

  • Tibbetts BM, Baden DG, Benson JM. Uptake, tissue distribution, and excretion of brevetoxin-3 administered to mice by intratracheal instillation. J Toxicol Environ Health A. 2006;69(14):1325–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trainer VL, Thomsen WJ, Catterall WA, Baden DG. Photoaffinity labeling of the brevetoxin receptor on sodium channels in rat brain synaptosomes. Mol Pharmacol. 1991;40(6):988–94.

    CAS  PubMed  Google Scholar 

  • Trainer VL, Baden DG, Catterall WA. Identification of peptide components of the brevetoxin receptor site of rat brain sodium channels. J Biol Chem. 1994;269(31):19904–9.

    CAS  PubMed  Google Scholar 

  • van Apeldorn ME, van Egmond HP, Speijers GJA. Neurotoxic shellfish poisoning: a review. RIVM Report 388802023. Bilthoven: National Institute for Public Health and the Environment; 2001. pp. 1–70.

    Google Scholar 

  • Wang Z, Ramsdell JS. Analysis of interactions of brevetoxin-B and human serum albumin by liquid chromatography/mass spectrometry. Chem Res Toxicol. 2011;24(1):54–64.

    Article  PubMed  Google Scholar 

  • Watkins M, Reich A, Fleming E, Hammond R. Neurotoxic shellfish poisoning. Mar Drugs. 2008;6:431–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Woofter RT, Ramsdell JS. Distribution of brevetoxin to lipoproteins in human plasma. Toxicon. 2007;49(7):1010–8.

    Article  CAS  PubMed  Google Scholar 

  • Woofter RT, Spiess PC, Ramsdell JS. Distribution of brevetoxin (PbTx-3) in mouse plasma: association with high-density lipoproteins. Environ Health Perspect. 2005;113(11):1491–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaias J, Fleming LE, Baden DG, Abraham WM. Repeated exposure to aerosolized brevetoxin-3 induces prolonged airway hyperresponsiveness and lung inflammation in sheep. Inhal Toxicol. 2011;23(4):205–11.

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Xu X, Li T, Liu Z. Shellfish toxins targeting voltage-gated sodium channels. Mar Drugs. 2013;11:4698–723.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Life Sciences, University of Trieste, Trieste, Italy

    Valentina Brovedani, Marco Pelin & Elisabetta D’Orlando

  2. U.S. Army Medical Research Institute of Infectious Diseases, Ft Detrick, MD, USA

    Mark Poli

Authors
  1. Valentina Brovedani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Pelin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elisabetta D’Orlando
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark Poli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Valentina Brovedani .

Editor information

Editors and Affiliations

  1. Dept of Anatomy, Natl Univ of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Universidade Estadual Paulista, Botucatu, São Paulo, Brazil

    Vidal Haddad Jr.

  3. Department of Life Sciences, University of Trieste, Trieste, Italy

    Aurelia Tubaro

  4. College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea (Republic of)

    Euikyung Kim

  5. College of Medicine, University of Florida, Gainesville, Florida, USA

    William R. Kem

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Dordrecht (outside the USA)

About this entry

Cite this entry

Brovedani, V., Pelin, M., D’Orlando, E., Poli, M. (2016). Brevetoxins: Toxicological Profile. In: Gopalakrishnakone, P., Haddad Jr., V., Tubaro, A., Kim, E., Kem, W. (eds) Marine and Freshwater Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6419-4_22

Download citation

Publish with us

Policies and ethics

Search

Navigation