brevetoxin and Ciguatera-Poisoning

Ciguatoxins (CTX) and brevetoxins (BTX) are polycyclic ethereal compounds biosynthesized by the worldwide distributed planktonic and epibenthic dinoflagellates of

Topics: Animals; Ciguatera Poisoning; Ciguatoxins; Dinoflagellida; Humans; Ligands; Marine Toxins; Oxocins; Potassium Channels, Voltage-Gated

Ciguatera fish poisoning arises from consumption of any of the 400 species of tropical marine reef fish containing polyether toxins. No laboratory method is available for clinical diagnosis of acute ciguatera poisoning. The objective of this pilot study was to ascertain the potential usefulness of a bioassay to detect ciguatoxins in humans suspected of acute intoxication. We analyzed plasma of healthy volunteers (asymptomatic negative controls), participants with gastrointestinal (GI) illness but without recent fish consumption (symptomatic negative controls), and participants with GI illness who had recently consumedfish.. Blood samples, questionnaires, and consent forms were collected from 11 symptomatic negative controls and 86 patients that visited emergency rooms in southern Puerto Rico over a 1-year period. Patients had consumed fish within 24 hour prior to the symptoms. Plasma samples were analyzed by a neuroblastoma cell bioassay that detects seafood toxins active at the sodium voltage-gated channel in a dose-dependent fashion. Concentrations were expressed in terms of brevetoxin-1 equivalents (ng PbTx-1 equiv/mL).. The mean plasma concentration of 14 asymptomatic negative controls was 39.4 ng PbTx-1 equiv/mL (range 2-74). Of 86 potential ciguatoxic patients who reported fish consumption, 43 had values within the range of normal volunteers, and 9 had concentrations in the nondiagnostic range (73.9-100 ng). Thirty-four patients (40%) had concentrations 3 standard deviations above asymptomatic negative controls (>100 ng PbTx-1 equiv/mL). They had a mean concentration of 1,074 +/- 244.5 ng PbTx-1 equiv/mL (range 101-7,056ng).. Preliminary findings of elevated PbTx-1 equivalents in 40% of the patients with both ciguatera symptomatology and fish consumption in a geographical area where ciguatera is common suggest that the neuroblastoma bioassay may be a potential diagnostic tool for acute ciguatera intoxication.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Animals; Biological Assay; Child; Child, Preschool; Ciguatera Poisoning; Ciguatoxins; Dose-Response Relationship, Drug; Female; Foodborne Diseases; Gastrointestinal Diseases; Humans; Infant; Male; Marine Toxins; Middle Aged; Neurotoxins; Oxocins; Pilot Projects; Puerto Rico; Tropical Climate

Ciguatera fish poisoning (CFP) and neurotoxic shellfish poisoning syndromes are induced by the consumption of seafood contaminated by ciguatoxins and brevetoxins. Both toxins cause sensory symptoms such as paresthesia, cold dysesthesia and painful disorders. An intense pruritus, which may become chronic, occurs also in CFP. No curative treatment is available and the pathophysiology is not fully elucidated. Here we conducted single-cell calcium video-imaging experiments in sensory neurons from newborn rats to study in vitro the ability of Pacific-ciguatoxin-2 (P-CTX-2) and brevetoxin-1 (PbTx-1) to sensitize receptors and ion channels, (i.e., to increase the percentage of responding cells and/or the response amplitude to their pharmacological agonists). In addition, we studied the neurotrophin release in sensory neurons co-cultured with keratinocytes after exposure to P-CTX-2. Our results show that P-CTX-2 induced the sensitization of TRPA1, TRPV4, PAR2, MrgprC, MrgprA and TTX-r NaV channels in sensory neurons. P-CTX-2 increased the release of nerve growth factor and brain-derived neurotrophic factor in the co-culture supernatant, suggesting that those neurotrophins could contribute to the sensitization of the aforementioned receptors and channels. Our results suggest the potential role of sensitization of sensory receptors/ion channels in the induction or persistence of sensory disturbances in CFP syndrome.

Topics: Animals; Animals, Newborn; Aquatic Organisms; Ciguatera Poisoning; Ciguatoxins; Marine Toxins; Models, Animal; Oxocins; Pacific Ocean; Pain; Pruritus; Rats; Rats, Wistar; Sensory Receptor Cells

Ciguatera fish poisoning and neurotoxic shellfish poisoning are distinct clinical entities characterized by gastrointestinal and neurological disturbances, following the consumption of certain reef fish and shellfish containing toxic polyether compounds sporadically present in certain toxic marine dinoflagellates. The biotransformation and bioaccumulation of gambierol and brevetoxin, and their congeners, are believed to be involved in the pathogenesis of these "food-chain diseases", for which no effective treatments are available. Here, we describe for the first time the potent effect of gambierol and brevetoxin on TRPV1 channels, a key player in thermal and pain sensation. Our findings may lead to promising new therapeutic interventions.

Topics: Animals; Ciguatera Poisoning; Ciguatoxins; Ethers, Cyclic; Humans; Marine Toxins; Oxocins; Patch-Clamp Techniques; Polycyclic Compounds; Shellfish; TRPV Cation Channels; Xenopus laevis

In Florida (USA), numerous cases of human ciguatera fish poisoning, as well as neurotoxic shellfish poisoning following consumption of local seafood products, have been reported. By using in parallel, the sodium channel receptor binding assay (RBA), and the ouabain/veratridine-dependent cytotoxicity assay (N2A assay), we established criteria to identify, detect, and quantify ciguatoxins in fish extracts, with a brevetoxin as internal standard. Results showed that the Caribbean ciguatoxin C-CTX-1 exhibited an 8-fold higher potency in the RBA than brevetoxins and, a 440 and 2300-fold higher potency in the N2A assay than PbTx-1 and PbTx-3, respectively. Moreover, a sensitivity comparison between assays revealed that the N2A assay was more sensitive (12-fold) for ciguatoxin analysis, whereas the RBA was more sensitive (3-24-fold) for brevetoxins analysis. Based on the relative potency between toxins and the opposite sensitivity of both assays we have used the RBA and the N2A assay to screen great barracuda (Sphyraena barracuda) collected from the Florida Keys for ciguatoxins and brevetoxins. Fish extract analysis showed a sodium channel-dependent activity consistent with the presence of ciguatoxins, and not brevetoxins. Among 40 barracudas analyzed, 60% contained ciguatoxin levels in their liver measurable by the N2A assay with the most toxic fish containing 2.1ppb C-CTX-1 equivalents.

Topics: Animals; Biological Assay; Cells, Cultured; Ciguatera Poisoning; Ciguatoxins; Fishes; Florida; Food Contamination; Humans; Lethal Dose 50; Marine Toxins; Ouabain; Oxocins; Protein Binding; Seawater; Sensitivity and Specificity; Sodium Channels; Veratridine

Topics: Adult; Air Pollutants; Animals; Caliciviridae Infections; Campylobacter Infections; Child; Ciguatera Poisoning; Cryptosporidiosis; Dinoflagellida; Disease Outbreaks; Fishes; Florida; Foodborne Diseases; Gastroenteritis; Giardiasis; Humans; Marine Toxins; Neurotoxins; Norwalk virus; Oxocins; Seafood; Seawater; Shellfish Poisoning; Vibrio Infections; Water Microbiology; Water Supply