| Natural and Derivative Brevetoxins: Historical Background, Multiplicity, and Effects Daniel G. Baden, Andrea J. Bourdelais, Henry Jacocks, Sophie Michelliza, and Jerome Naar University of North Carolina at Wilmington, Center for Marine Science, Wilmington, North Carolina, USA Abstract
Symptoms consistent with inhalation toxicity have long been associated with Florida red tides, and various causal agents have been proposed. Research since 1981 has centered on a group of naturally occurring trans-fused cyclic polyether compounds called brevetoxins that are produced by a marine dinoflagellate known as Karenia brevis. Numerous individual brevetoxins have been identified from cultures as well as from natural bloom events. A spectrum of brevetoxin derivatives produced by chemical modification of the natural toxins has been prepared to examine the effects of functional group modification on physiologic activity. Certain structural features of natural and synthetic derivatives of brevetoxin appear to ascribe specific physiologic consequences to each toxin. Differential physiologic effects have been documented with many of the natural toxins and derivatives, reinforcing the hypothesis that metabolism or modification of toxin structures modulates both the specific toxicity (lethality on a per milligram basis) and potentially the molecular mechanism(s) of action. A series of naturally occurring fused-ring polyether compounds with fewer rings than brevetoxin, known as brevenals, exhibit antagonistic properties and counteract the effects of the brevetoxins in neuronal and pulmonary model systems. Taken together, the inhalation toxicity of Florida red tides would appear to depend on the amount of each toxin present, as well as on the spectrum of molecular activities elicited by each toxin. Toxicity in a bloom is diminished by the amount brevenal present. Key words: brevenal, brevetoxin, Florida red tide, immunotoxicant, Karenia brevis, neurotoxin, PbTx, polyether, pulmonary toxicant. Environ Health Perspect 113:621-625 (2005) . doi: 10.1289/ehp.7499 available via http: //dx.doi.org/ doi:10.1289/ehp.7499 available via http://dx.doi.org/ [Online 10 February 2005]
This article is part of the mini-monograph "Aerosolized Florida Red Tide Toxins (Brevetoxins) ." Address correspondence to D.G. Baden, Center for Marine Science, UNCW, 5600 Marvin Moss Lane, Wilmington, NC 28409 USA. Telephone: (910) 962-2408. Fax: (910) 962-2405. E-mail: baden@uncw.edu We thank the Harmful Algal Bloom Laboratory for Analytical Biotechnology (HABLAB) at UNCW, technicians S. Niven, J. Lamberto, L. Tomas, and E. McConnell, and colleagues C. Tomas and J.L.C. Wright. Grant support is acknowledged from National Institute of Environmental Health Sciences grants R01 ES05853, R01 ES 06411, and P01 ES 10594. The authors declare a competing financial interest concerning brevenal. D.G. Baden and A.J. Bourdelais are named in a patent application for uses of brevenal in mucociliary disease treatment. Received 2 August 2004 ; accepted 9 February 2005.
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