Ciguatoxin Pacific

Lewis, R.J., Jones, A. and Vemoux, J.P., HPLC/tandem electrospray mass spectrometry for the determination of Sub-ppb levels of Pacific and Caribbean ciguatoxins in crude extracts of fish. Anal. Chem., 71, 1, 247, 1999. 

Nakajlma and coworkers (20) reported an ether soluble extract from concavum to be slightly toxic to mice but provided little additional information. Crude fractions containing ciguatoxin obtained from moray eel (Gymnothorax javanicus) and toxlcus from the Pacific were reported to have LD q s of 12.2 mg/kg and 28.1 mg/kg, respectively (37). These compare well with the LD q of 8.3 mg/kg for similarly purified ESAF from concavum. 

A dinoflagellate, Gambierdiscus toxicus has been reported to be the likely progenitor of ciguatoxin in the South Pacific (13-15). Recently, Tindall, (26), Miller, ]]) and Carlson, (18) reported on toxic extracts from G. toxicus and two species of Prorocentrum from the Caribbean. iHe physiological action of toxic extracts from G, toxicus were found to be similar to those induced by toxic extract from Scomberomorus cavalla (Kingfish) from the same region (19). 

Relationship of Fractions to Other Toxins. Our initial extractions of tHe toxic fractions are tHe same as that of Tachibana, ( ) and others. Thus, the isolation of GT-la and GT-lb correspond exactly to the initial steps in the isolation of ciguatoxin by Scheuer ( ). The isolation of GT-2b and GT-2c and their similar action on the ileum preparation, causes us to conclude that they are either a more polar form of GT-1 or a modification of GT-1 accomplished during the extraction procedures. GT-3, it appears, would most likely correspond to a carry over of a maitotoxin-1ike fraction from the initial ether-water separation. Without any chemical confirmation, however, these are only tentative identifications. Indeed, toxins extracted from Caribbean isolates of toxicus, could be quite different from those extracted from Pacific isolates. 

Ciguatoxin (CTX) is the major chemical entity associated with ciguatera fish poisoning. CTX, a term given to the low dalton lipid by Scheuer et al. (JL) was isolated from livers of Gymnothorax obtained from an endemic area in the Pacific. A recent study by Tachibana ( 2) in Scheuer s laboratory suggests that CTX consists of numerous cyclic polyether residues similar to okadaic acid (3-5) and monensin ( ). ... 

Source of Extracted Fish Toxin. Two different extracts of ciguatoxic fish were used in this study. Partially purified ciguatoxin was derived from the liver and viscera of the Pacific moray eel (Gymnothorax Javanicus) and was a side fraction of the... 

AU marine polyether ladders thus far characterized (e.g., maito-toxin 16 (Fig. 4a), the brevetoxins 12 and 13 and hemibreve-toxin B, the yessotoxins 14 (and the truncated adriatoxin), the Pacific and Caribbean ciguatoxins, the gambieric acids 15 and gamberiol (the gymnocins and brevenal) can be grouped into 14 backbone structures (3). 

PbTx-1, PbTx-2, PbTx-3 metabolites BTX-Bl, BTX-B2, deoxyBTX-B2, BTX-B4, BTX-B5 Caribbean ciguatoxins C-CTX-1, C-CTX-2 Pacific ciguatoxins P-CTX-1, P-CTX-2, P-CTX-3... 

Hidalgo, J. et al., Pacific ciguatoxin-lb effect over Na and currents, inositol 1,4,5-triphosphate content and intracellular Ca signals in cultured rat myotubes, Br 7 Pharmacol 137, 1055, 2002. 

Ciguatoxins in finfish comprise an assemblage of principal ciguatoxins and numerous closely related structural isomers and congeners. The Pacific ciguatoxins were structurally characterized before the Caribbean ciguatoxins, and the latter differ slightly in structure and toxicity. Both Pacific... 

FIGURE 22.2 Principal Pacific (P-CTX-1) and Caribbean (C-CTX-1) fish ciguatoxin structures. 

FIGURE 22.8 In vitro cell assay of (a) Pacific ciguatoxin P-CTX-1 reference standard, and (b) Pacific cigua-toxicosis case sample 061001 (C. miniata). 

Hidalgo, J. et al.. Pacific ciguatoxin-lb effect over Na and K currents, inositol 1,4,5-triphosphate content and intracellular Ca signals in cultured rat myotubes, Br. J. Pharmacol, 137, 1055, 2002. Birinyi-Strachan, L.C. et al.. Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons, Toxicol. Appl. Pharmacol, 204, 175, 2005. 

Campora, C.E., Hokama, Y. and Ebesu, J.S., Comparative analysis of purified Pacific and Caribbean ciguatoxin congeners and related marine toxins using a modified ELISA technique, J. Clin. Lab. Anal., 20, 121, 2006. 

Abbreviations UV, ultraviolet EIA, enzyme immunoassay S-PIA, solid-phase immunobead assay P-CTX-1, Pacific ciguatoxin-1 C-CTX-1, Caribbean ciguatoxin-1 EC50, half maximally effective concentration. 

CEP is associated with the consumption of many species of tropical and subtropical fish contaminated by ciaguatoxins, a family of lipid-soluble, heat-stable molecules (Figure 3) produced by the benthic dinoflagellate Gamberdierdiscus toxicus. Pacific ciguatoxin-1 (P-CTX-1) and Caribbean ciguatoxin-1 (C-CTX-1) are the major toxins contributing to CEP, and are usually considered the main... 

Sauviat, M.-R, Boydron-Le Garrec, R., Masson, J.-B. et al. 2006. Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins. Blood Cell. Mol. Dis. 36 1-9. 

Hoffman et al. (1983) constructed a dose-response curve for purified ciguatoxin obtained from toxic blackfin snapper collected from the Virgin Islands. A m-ptomatological analysis was reported that would facilitate the comparison among reports on ciguatera research. The mouse bioassay has been used extensively in the Pacific and is described in detail by Yasumoto et al. (1984). 

Oshika H (1971) Marine toxins from the Pacific IX. Some effects of ciguatoxin on isolated manunalian atria. Toxicon 9 337-343. 

Yasumoto T, Scheuer PJ (1969) Marine toxins from the Pacific-VEQ ciguatoxin from moray eel livers. Toxicon, 7 273-276. 

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