Skip to main content
SpringerLink
Log in

Toxic potential of palytoxin

  • Published:
Journal of Huazhong University of Science and Technology [Medical Sciences] Aims and scope Submit manuscript

Summary

This review briefly describes the origin, chemistry, molecular mechanism of action, pharmacology, toxicology, and ecotoxicology of palytoxin and its analogues. Palytoxin and its analogues are produced by marine dinoflagellates. Palytoxin is also produced by Zoanthids (i.e. Palythoa), and Cyanobacteria (Trichodesmium). Palytoxin is a very large, non-proteinaceous molecule with a complex chemical structure having both lipophilic and hydrophilic moieties. Palytoxin is one of the most potent marine toxins with an LD50 of 150 ng/kg body weight in mice exposed intravenously. Pharmacological and electrophysiological studies have demonstrated that palytoxin acts as a hemolysin and alters the function of excitable cells through multiple mechanisms of action. Palytoxin selectively binds to Na+/K+-ATPase with a Kd of 20 pM and transforms the pump into a channel permeable to monovalent cations with a single-channel conductance of 10 pS. This mechanism of action could have multiple effects on cells. Evaluation of palytoxin toxicity using various animal models revealed that palytoxin is an extremely potent neurotoxin following an intravenous, intraperitoneal, intramuscular, subcutaneous or intratracheal route of exposure. Palytoxin also causes non-lethal, yet serious toxic effects following dermal or ocular exposure. Most incidents of palytoxin poisoning have manifested after oral intake of contaminated seafood. Poisonings in humans have also been noted after inhalation, cutaneous/systemic exposures with direct contact of aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing Cnidarian zoanthids. Palytoxin has a strong potential for toxicity in humans and animals, and currently this toxin is of great concern worldwide.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Moore RE, Scheuer PJ. Palytoxin: a new marine toxin from a coelenterate. Science, 1971,172(3982):495–498

    Article  CAS  PubMed  Google Scholar 

  2. Deeds JR, Schwartz MD. Human risk associated with palytoxin exposure. Toxicon, 2010,56(2):150–162

    Article  CAS  PubMed  Google Scholar 

  3. Carballeira NM, Emiliano A, Sostre A, et al. Fatty acid composition of bacteria associated with the toxic dinoflagellate Ostreopsis lenticularis and with Caribbean Palythoa species. Lipids, 1998,33(6):627–632

    Article  CAS  PubMed  Google Scholar 

  4. Tubaro A, Sosa S, Hungerford J. Toxicology and diversity of marine toxins. In: Gupta RC, ed. Veterinary Toxicology: Basic and Clinical Principles. Amsterdam: Academic Press/Elsevier, 2012, 896–934

    Chapter  Google Scholar 

  5. Aligizaki K, Katikou P, Milandri A, et al. Occurrence of palytoxin-group toxins in seafood and future strategies to complement the present state of the art. Toxicon, 2011,57(3):390–399

    Article  CAS  PubMed  Google Scholar 

  6. Munday R. Palytoxin toxicology: Animal studies. Toxicon, 2011,57(3):470–477

    Article  CAS  PubMed  Google Scholar 

  7. EFSA. Scientific opinion on marine biotoxins in shellfish–palytoxin group. EFSA J, 2009,1393(1):1–38

  8. Wu CH. Palytoxin: membrane mechanisms of action. Toxicon, 2009,54(8):1183–1189

    Article  CAS  PubMed  Google Scholar 

  9. Rossini GP, Bigiani A. Palytoxin action on the Na(+),K(+)-ATPase and the disruption of ion equilibria in biological systems. Toxicon, 2011,57(3):429–439

    Article  CAS  PubMed  Google Scholar 

  10. Weidmann S. Effects of palytoxin on the electrical activity of dog and rabbit heart. Experientia, 1977,33(11):1487–1489

    Article  CAS  PubMed  Google Scholar 

  11. Rossini GP, Bigiani A. Palytoxin action on the Nat,Kt- ATPase and the disruption of ion equilibria in biological systems. Toxicon, 2011,57(3):429–439

    Article  CAS  PubMed  Google Scholar 

  12. Frelin C, Van Renterghem C. Palytoxin. Recent electrophysiological and pharmacological evidence for several mechanisms of action. Gen Pharmacol, 1995,26(1): 33–37

    Article  CAS  PubMed  Google Scholar 

  13. Artigas P, Gadsby DC. Large diameter of palytoxininduced Na/K pump channels and modulation of palytoxin interaction by Na/K pump ligands. J Gen Physiol, 2004,123(4):357–376

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Haberman E. Palytoxin acts through Na+/K-ATPase. Toxicon, 1989,27(6):1171–1187

    Article  Google Scholar 

  15. Ares IR, Louzao MC, Vieytes MR, et al. Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins. J Exp Biol, 2005,208(22):4345–4354

    Article  CAS  PubMed  Google Scholar 

  16. Shimizu Y. Structural chemistry: Complete structure of palytoxin elucidated. Nature, 1983,302(1):112

    Google Scholar 

  17. Moore RE. Structure of palytoxin. Fortschr Chem Org Naturst, 1985,48(1):81–202

    CAS  PubMed  Google Scholar 

  18. Riobó P, Franco JM. Palytoxins: Biological and chemical determination. Toxicon, 2011,57(3):368–375

    Article  PubMed  Google Scholar 

  19. Ciminiello P, Dell'Aversano C, Dello Iacovo E, et al. LCMS of palytoxin and its analogues: state of the art and future perspectives. Toxins, 2011,57(3):376–389

    CAS  Google Scholar 

  20. Munday R. Palytoxin toxicology: animal studies. Toxicon, 2011,57(3):470–477

    Article  CAS  PubMed  Google Scholar 

  21. Kita M, Uemura D. Marine huge molecules: the longest carbon chains in natural products. Chem Rec, 2010,10(1):48–52

    Article  CAS  PubMed  Google Scholar 

  22. Moore RE, Bartolini G, Barchi J, et al. Absolute stereochemistry of palytoxin. J Am Chem Soc, 1982,104(13):3776–3779

    Article  CAS  Google Scholar 

  23. Ramos V, Vasconcelos V. Palytoxin and analogs: biological and ecological effects. Mar Drugs, 2010,8(7):2021–2037

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Fernández DA, Louzao MC, Vilariño N, et al. The kinetic, mechanistic and cytomorphological effects of palytoxin in human intestinal cells (Caco-2) explain its lower-thanparenteral oral toxicity. FEBS J, 2013,280(16):3906–3919

    Article  PubMed  Google Scholar 

  25. Ciminiello P, Dell'Aversano C, Fattorusso E, et al. The Genoa 2005 outbreak. Determination of putative palytoxin in Mediterranean Ostreopsis ovata by a new liquid chromatography tandem mass spectrometry method. Anal Chem, 2006,78(17):6153–6159

    Article  CAS  PubMed  Google Scholar 

  26. Riobó P, Paz B, Franco JM. Analysis of palytox-in-like in Ostreopsis cultures by liquid chromatography with precolumn derivatization and fluorescence detection. Anal Chim Acta, 2006,566(2):217–223

    Article  Google Scholar 

  27. Monti M, Minocci M, Beran A, Ivena L. First record of Ostreopsis cfr Ovata on macroalgae in the northern Adriatic. Sea. Mar Pol Bull, 2007,54(5):598–601

    Article  CAS  Google Scholar 

  28. Aligizaki K, Panagiota K, Nikolaidis G, et al. First episode of shellfish contamination by palytoxin-like compounds from Ostreopsis species (Aegean Sea, Greece). Toxicon, 2008,51(3):418–427

    Article  CAS  PubMed  Google Scholar 

  29. Rhodes L. World-wide occurrence of the toxic dinoflagellate genus oxytropsis Schmidt. Toxicon, 2011,57(3):400–407

    Article  CAS  PubMed  Google Scholar 

  30. Katikou P. Palytoxin and analogues: etiology and origin, chemistry, metabolism, and chemical analysis. In: Botana LM, ed. Seafood and Freshwater Toxins: Pharmacology, Physiology and Detection. Boca Raton: CRC Press, 2008, 631–663

    Chapter  Google Scholar 

  31. Ciminiello P, Dell'Aversano C, Dello Iacovo, et al. Complex palytoxin-like profile of Ostreopsis ovata. Identification of four new ovatoxins by high-resolution liquid chromatography/mass spectrometry. Rapid Commun Mass Spectrom, 2010,24(18):2735–2744

    Article  CAS  PubMed  Google Scholar 

  32. Tichadou L, Glaizal M, Armengaud A, et al. Health impact of unicellular algae of the Ostreopsis genus blooms in the Mediterranean Sea: experience of the French Mediterranean coast surveillance network from 2006 to 2009. Clin Toxicol, 2010,48(8):839–844

    Article  Google Scholar 

  33. Sansoni G, Borghini B, Camici G, et al. Fioriture algali di Ostreopsis Ovata (Gonyaulacales: Dinophyceae): Unproblema emergente. Biol Ambientale, 2003,17(1):17–23

    Google Scholar 

  34. Gallitelli M, Ungaro N, Addante LM, et al. Respiratory illness as a reaction to tropical algal bloom occurring in a temperate climate. J Am Med Assoc, 2005,293(21):2599–2600

    CAS  Google Scholar 

  35. Louzao MC, Ares IR, Vieytes MR, et al. The cytoskeleton, a structure that is susceptible to the toxic mechanism activated by palytoxins in human excitable cells. FEBS J, 2007,274(8):1991–2004

    Article  CAS  PubMed  Google Scholar 

  36. Gleibs S, Mebs D. Distribution and sequestration of palytoxin in coral reef animals. Toxicon, 1999,37(11): 1521–1527

    Article  CAS  PubMed  Google Scholar 

  37. Harmel N, Apell HJ. Palytoxin-induced effects on partial reactions of the Na,K-ATPase. J Gen Physiol, 2006,128(1):103–118

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Rodrigues AM, Infantosi AF, de Almeida AC. Palytoxin and the sodium/potassium pump—phosphorylation and potassium interaction. Phys Biol, 2009,6(3):036010

    Article  PubMed  Google Scholar 

  39. Vedovato N, Gadsby DC. The two C-terminal tyrosines stabilize occluded Na/K pump conformations containing Na or K ions. J Gen Physiol, 2010,136(1):63–82

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Redondo J, Fiedler B, Scheiner-Bobis G. Palytoxininduced Na+ influx into yeast cells expressing the mammalian sodium pump is due to the formation of a channel within the enzyme. Mol Pharmacol, 1996,49(1):49–57

    CAS  PubMed  Google Scholar 

  41. Louzao MC, Ares IR, Cagide E. Marine toxins and the cytoskeleton: a new view of palytoxin toxicity. FEBS J, 2008,275(24):6067–6074

    Article  CAS  PubMed  Google Scholar 

  42. Del Favero G, Beltramo D, Onidi M, et al. Acute oral toxicity of Palytoxin and Okadaic acid in mice. Toxicol Lett, 2012,21(1):S157-S158

    Google Scholar 

  43. Tatsumi M, Takahashi M, Ohizumi Y. Mechanism of palytoxin-induced [3H]norepinephrine release from a rat pheochromocytoma cell line. Mol Pharmacol, 1984,25(3): 379–383

    CAS  PubMed  Google Scholar 

  44. Yoshizumi Y, Nakanishi A, Houchi H, et al. Characterization of palytoxin-induced catecholamine secretion from cultured bovine adrenal chromaffin cells. Effects of Na+- and Ca2+-channel blockers. Biochem Pharmacol, 1991,42(1):17–23

    Article  CAS  PubMed  Google Scholar 

  45. Satoh E, Nakazato Y. Mode of action of palytoxin on the release of acetylcholine from rat cerebrocrtical synaptosomes. J Neurochem, 1991,57(4):1276–1280

    Article  CAS  PubMed  Google Scholar 

  46. Crinelli R, Carloni E, Giaconini E, et al. Palytoxin and an Ostreopsis toxin extract increase the levels of mRNAs encoding inflammation-related proteins in human macrophages via p38 MAPK and NF-κB. PloS One, 2012,7(6): e38139

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  47. Ito K, Urakawa N, Koike H. Cardiovascular toxicity of palytoxin in anesthetized dogs. Arch Intl de Pharmacod et de Ther, 1982,258(1):146–154

    CAS  Google Scholar 

  48. Sosa S, Del Favero G, De Bortoli M, et al. Palytoxin toxicity after acute oral administration in mice. Toxicol Lett, 2009,191(2–3):253–259

    Article  CAS  PubMed  Google Scholar 

  49. Ito E, Ohkusu M, Yasumoto T. Intestinal injuries caused by experimental palytoxicosis in mice. Toxicon, 1996,34(6):643–652

    Article  CAS  PubMed  Google Scholar 

  50. Ito E, Yasumoto T. Toxicological studies on palytoxin and ostreocin-D administered to mice by three different routes. Toxicon, 2009,54(3):244–251

    Article  CAS  PubMed  Google Scholar 

  51. Ramos V, Vasconcelos V. Palytoxin and analogs: biological and ecological effects. Mar Drugs, 2010,8(7):2021–2037

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Fujiki H, Suganuma M, Nakayasu M, et al. Palytoxin is a non 12-O-tetradecanoylphorbol-13-acetate type tumor promotor in two-stage skin carcinogenesis. Carcinogenesis, 1986,7(5):707–710

    Article  CAS  PubMed  Google Scholar 

  53. Terao K, Ito E, Yasumoto T. Light and electron microscopic observation of experimental palytoxin poisoning in mice. Bull Soc Pathol Exot, 1992,85(5):494–496

    CAS  PubMed  Google Scholar 

  54. Del Favero G, Beltramo D, Sciancalepore M, et al. Toxicity of palytoxin after repeated oral exposure in mice and in vitro effects on cardiomyocytes. Toxicon, 2013,75(1):3–15

    Article  PubMed  Google Scholar 

  55. Pelin M, Sosa S, Pacor S, et al. The marine toxin palytoxin induces necrotic death in HaCaT cells through a rapid mitochondrial damage. Toxicol Lett, 2014,229(3):440–450

    Article  CAS  PubMed  Google Scholar 

  56. Tubaro A, Del Favero G, Beltramo D, et al. Acute oral toxicity in mice of a new oalytoxin analog: 42-hydroxypalytoxin. Toxicon, 2011,57(5):755–763

    Article  CAS  PubMed  Google Scholar 

  57. Tubaro A, Durando P, Del Favero G, et al. Case definitions for human poisonings postulated to palytoxins exposure. Toxicon, 2011,57(3):478–495

    Article  CAS  PubMed  Google Scholar 

  58. Forino M, Ciminiello P, Fattorusso E, et al. Palytoxins: a still haunting Hawaiian curse. Pytochem Rev, 2010,9(4):491–500

    Article  Google Scholar 

  59. Wattenberg EV, Fujiki H, Rosner MR. Heterologous regulation of the epidermal growth factor receptor by palytoxin, anon-12-O-tetradecanoylphorbol-13-acetatetype tumor promoter. Cancer Res, 1987,47(17):4618–4622

    CAS  PubMed  Google Scholar 

  60. Rumore MM, Houst BM. Palytoxin poisoning via inhalation in pediatric siblings. Int J Case Rep Images, 2014,5(7):501–504

    Article  Google Scholar 

  61. Tubaro A, Durando P, Del Favero G, et al. Case definitions for human poisonings postulated to palytoxins exposure. Toxicon, 2011,57(3):478–495

    Article  CAS  PubMed  Google Scholar 

  62. Hoffmann K, Hermanns-Clausen M, Buhl C, et al. A case of palytoxin poisoning due to contact with zoanthid corals through skin injury. Toxicon, 2008,51(8):1535–1537

    Article  CAS  PubMed  Google Scholar 

  63. Alcala AC, Alcala LC, Garth JS, et al. Human fatality due to ingestion of the crab Demania reynaudii that contained a palytoxin-like toxin. Toxicon, 1988,26(1):105–107

    Article  CAS  PubMed  Google Scholar 

  64. Granéli E, Ferreira CEL, Yasumoto T, et al. Sea urchins poisoning by the benthic dinoflagellate Ostreopsis ovata on the Brazilian coast. In: Book of Abstracts of Xth International Conference on Harmful Algae. St. Petersburg, Florida. 2002

    Google Scholar 

  65. Fukui M, Murata M, Inoue A, et al. Occurrence of palytoxin in the trigger fish Melichtys vidua. Toxicon, 1987,25(10):1121–1124

    Article  CAS  PubMed  Google Scholar 

  66. Okano H, Masuoka H, Kamei S, et al. Rhabdomyolysis and myocardial damage induced by palytoxin, a toxin of blue humphead parrotfish. Int Med, 1998,37(3):330–333

    Article  CAS  Google Scholar 

  67. Onuma Y, Satake M, Ukena T, et al. Identification of putative palytoxin as the cause of clupeotoxism. Toxicon, 1999,37(1):55–65

    Article  CAS  PubMed  Google Scholar 

  68. Béress L, Zwick J, Kolkenbrock HJ, et al. A method for the isolation of the caribbean palytoxin (C-PTX) from the coelenterate (zooanthid) Palythoa caribaeorum. Toxicon, 1983,21(2):285–290

    Article  PubMed  Google Scholar 

  69. Nordt SP, Wu J, Zahller S, et al. Palytoxin poisoning after dermal contact with Zoanthid coral. J Emerg Med, 2009,40(4):397–399

    Article  PubMed  Google Scholar 

  70. Vasconcelos V, Ramos V. Palytoxin and analogs: Biological and ecological effects. Mar Drugs, 2010,8(7):2021–2037

    Article  PubMed Central  PubMed  Google Scholar 

  71. Yoshimine K, Orita S, Okada S, et al. Two cases of parrotfish poisoning with rhabdomyolysis. Nippon Naika Gakkai Zasshi, 2001,90(7):1339–1341

    Article  CAS  PubMed  Google Scholar 

  72. EFSA (European Food Safety Authority). Scientific opinion on marine biotoxins in shellfish-palytoxin group. EFSA J, 2009,1393:1–38

  73. Rhodes L, Munday R, Briggs L. Ostreopsis siamensis and palytoxin-related compounds in New Zealand: a risk to human health? In: Moestrup Ø, ed. Proceedings of the 12th International Conference on Harmful Algae., Copenhagen: ISSHA and Intergovernmental Oceanographic Commision of UNESCO, 2008:326–329

    Google Scholar 

  74. Majlesi N, Su MK, Chan GM, et al. A case of inhalation exposure to palytoxin. Clin Toxicol, 2008,46(1):673

    Google Scholar 

  75. Wiles J, Vick J, Christensen M. Toxicological evaluation of palytoxin in several animal species. Toxicon, 1974,12(4):427–433

    Article  CAS  PubMed  Google Scholar 

  76. Mebs D. Occurrence and sequestration of toxins in food chains. Toxicon, 1998,36(11):1519–1522

    Article  CAS  PubMed  Google Scholar 

  77. Kaul PN, Daftari P. Marine pharmacology: bioactive molecules from the sea. Annu Rev Pharmacol Toxicol, 1986,26(1):117–142

    Article  CAS  PubMed  Google Scholar 

  78. Mahnir VM, Kozlovskaya EP, Kalinovsky AI. Sea anemone Radianthus macrodactylus—a new source of palytoxin. Toxicon, 1992,30(11):1449–1456

    Article  CAS  PubMed  Google Scholar 

  79. Webber HH, Ruggieri GD. Food-Drugs from the Sea. In: Proceedings of the Conference, 4th, Mayaguez, 1974. Washington, DC: Marine Technology Soc, 1974, 311

    Google Scholar 

  80. Vick JA, Wiles JS. The mechanism of action and treatment of palytoxin poisoning. Toxicol Appl Pharmacol, 1975,34(2):214–223

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of South Bohemia Ceske Budejovice, Faculty of Health and Social Studies, Department of Radiology and Toxicology, Ceske Budejovice, 37005, Czech Republic

    Jiří Patocka

  2. Biomedical Research Center, University Hospital, Hradec Kralove, 50003, Czech Republic

    Jiří Patocka & Kamil Kuca

  3. Toxicology Department, Murray State University, Hopkinsville, 42071, USA

    Ramesh C. Gupta

  4. College of Life Science, Yangtze University, Jingzhou, 434025, China

    Qing-hua Wu  (吴庆华)

  5. Faculty of Informatics and Management, University of Hradec Kralove, Hradec Kralove, 50003, Czech Republic

    Qing-hua Wu  (吴庆华) & Kamil Kuca

Authors
  1. Jiří Patocka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ramesh C. Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qing-hua Wu  (吴庆华)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kamil Kuca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Qing-hua Wu  (吴庆华) or Kamil Kuca.

Additional information

This work was supported by Long Term Development Plan of University Hospital Hradec Kralove and University of Hradec Kralove, the Project of Excellence FIM UHK, as well as, Yangtze Youth Talents Fund (Yangtze University).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Patocka, J., Gupta, R.C., Wu, Qh. et al. Toxic potential of palytoxin. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 773–780 (2015). https://doi.org/10.1007/s11596-015-1506-3

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11596-015-1506-3

Key words

Search

Navigation