The major focus of this Project has been to examine the potential adverse health effects resulting from prolonged inhalation exposure to brevetoxins. The inhalation toxicities of a complex mixture of brevetoxins and brevetoxin antagonists in K. brevis extract was examined in rats, and the toxicity of pure brevetoxin 3 was examined in both rats and mice. Substantial immune suppression in rats, as indicated by a reduction in antibody response to immunization with sheep red blood cells, was consistently the primary response observed. Suppression of antibody forming responses occurred in the absence of frank toxicity to the spleen, changes in lymphocyte populations, or T cell responses to antigen. This immune suppression is important in light of reports in increased emergency room visits for pneumonia during Red Tide episodes identified by Fleming project and decreases in alveolar macrophage function in sheep inhaling brevetoxins in project by Abraham. This proposal will address the following specific aims: (1) To define exposure concentration-response relationships for brevetoxin-induced effects on humoral immunity in rats and to examine the role of macrophage cathepsin inhibition in mediating these effects;(2) To examine the effects of brevetoxin inhalation on recovery from infection in a rat model of influenza including young adult and aged rats;and (3) To determine the immunotoxic potential of brevetoxin in offspring of dams inhaling brevetoxins. These investigations will broaden examination of the exposure concentration-response relationship for brevetoxin-induced effects on antibody responses to antigen, provide insight into the underlying mechanism(s) for the observed immune suppression, examine potential consequences to brevetoxin-induced immune suppression on responses to viral infection; and determine the potential developmental immunotoxicity resulting from perinatal brevetoxin exposure.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
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University of North Carolina Wilmington
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McCall, Jennifer R; Goodman, Allan J; Jacocks, Henry M et al. (2014) Development of a fluorescence assay for the characterization of brevenal binding to rat brain synaptosomes. J Nat Prod 77:2014-20
McCall, Jennifer R; Jacocks, Henry M; Niven, Susan C et al. (2014) Development and utilization of a fluorescence-based receptor-binding assay for the site 5 voltage-sensitive sodium channel ligands brevetoxin and ciguatoxin. J AOAC Int 97:307-15
Goodman, Allan; McCall, Jennifer R; Jacocks, Henry M et al. (2014) Structure activity relationship of brevenal hydrazide derivatives. Mar Drugs 12:1839-58
Gold, Elena P; Jacocks, Henry M; Bourdelais, Andrea J et al. (2013) Brevenal, a brevetoxin antagonist from Karenia brevis, binds to a previously unreported site on mammalian sodium channels. Harmful Algae 26:12-19
McCall, Jennifer R; Jacocks, Henry M; Baden, Daniel G et al. (2012) Development of a competitive fluorescence-based synaptosome binding assay for brevetoxins. Harmful Algae 19:85-91
Zhou, Yue; Sun, Jaijie; Cheng, Yung-Sung (2011) Comparison of deposition in the USP and physical mouth-throat models with solid and liquid particles. J Aerosol Med Pulm Drug Deliv 24:277-84
Bean, Judy A; Fleming, Lora E; Kirkpatrick, Barbara et al. (2011) Florida Red Tide Toxins (Brevetoxins) and Longitudinal Respiratory Effects in Asthmatics. Harmful Algae 10:744-748
Benson, Janet M; Wolf, Molly L; Kajon, Adriana et al. (2011) Brevetoxin inhalation alters the pulmonary response to influenza A in the male F344 rat. J Toxicol Environ Health A 74:313-24
Murrell, Rachel N; Gibson, James E (2011) Brevetoxin 2 alters expression of apoptotic, DNA damage, and cytokine genes in Jurkat cells. Hum Exp Toxicol 30:182-91
Fleming, Lora E; Kirkpatrick, Barbara; Backer, Lorraine C et al. (2011) Review of Florida Red Tide and Human Health Effects. Harmful Algae 10:224-233

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