Reversal of Pacific ciguatoxin-1B effects on myelinated axons by agents used in ciguatera treatment

Ciguatera fish poisoning is a distinctive form of ichthyosarcotoxism charac terised mainly by gastrointestinal and neurological disturbances. The cigua toxins, responsible for this poisoning, are complex polyethers produced by toxic strains of the dinoflagellate Gambierdiscus toxicus. These toxins are increased to dangerous levels for man during their transmission through he rbivorous and carnivorous fish, various species being contaminated. The kno wn molecular target of ciguatoxins is the voltage-gated Na+ channel. During the action of these toxins, the permanent opening of channels, at the rest ing membrane potential, produces a continuous entry of Naf ions in excitabl e cells causing a marked increase in membrane excitability and in cellular volume. To precise the neurocellular basis of the efficacy of some agents u sed in clinical and traditional treatments of ciguatera, their effects were studied on frog myelinated axons exposed to Pacific ciguatoxin-1B (CTX-1B) . During the action of this toxin, the increase in axonal volume and membra ne excitability was reversed by lidocaine (a local anaesthetic), by CaCl2 a nd by hyperosmotic external solutions (containing D-mannitol, sucrose or te tramethylammonium chloride). The CTX-1B-induced hyperexcitability of the me mbrane was also reversed by extracts of Argusia argentea leaves or Davallia solida rhizomes, used traditionally in New-Caledonia. It is concluded that the various agents studied are able to counteract the neurocellular effect s of CTX-1B in myelinated axons. These results are of particular interest s ince they provide a scientific basis to understand the beneficial action of therapeutic agents used in the treatment of ciguatera fish poisoning.