## 6 Discussion and Perspectives
### Multiplicity of Caribbean Cgiuotoxins
A notable observation from studying toxin profiles [23; 41; 42; 108; 131] is that in the most toxic fish, at the limit of edibility or inedible, C-CTX-1 appears to be predominant. Among the 12 samples of _Caranax latus_, the highest relative levels of C-CTX-1 (\(\sim\)75-90%) were observed in low toxic specimens. Their slight losses of activity during the purification stage indicated that unstable CTXs were not present [42]. In contrast, highly toxic horse-eye jacks had relatively low levels of C-CTX-1 (\(\sim\)50%) and were subject to larger toxicity losses upon purification, indicating that relatively high levels of unstable CTXs were present [42]. In a highly ciguotoxic barracuda from Guadeloupe, two distinct fractions were purified depending on symptomatology in mice. C-CTX-1 accounted for \(\sim\)90% of the total toxicity (49 ppb in first fraction). However, despite important losses in toxicity (>60%) during purification of the second fraction, peak of sodium channel activity was identified, and two pseudo-molecular ions at \(m/z\) 809.43 and \(m/z\) 857.42 were detected using LC-MS. In a barracuda associated with a CP, C-CTX-1 contributed to \(\sim\)60% of the toxicity found using CBA-N2a [108]. In fish from Macaronesia, C-CTX-1 was detected in the CTX-like active fractions exhibiting the highest toxicity [130; 175], which represented more than 60% of the total toxin content (0.16 to 0.56 ppb), followed by 17-hydroxy-C-CTX-1 (0.11 to 0.23 ppb) in four fish [131]. However, these results must be analysed with caution, as these studies mostly evaluated variable percentages of congeners (or groups of isomers with the same molecular weight) depending on the fish and their total toxicity [42]. Thus, the relative percentages considered all the putative C-CTXs identified through LC-MS or LC-MS/MS analyses, whereas the data on their in vitro and/or in vivo toxicity compared to that of C-CTX-1 are still lacking. Finally, the recent discovery by [PERSON] et al. of C-CTX-5 (1138.6 Da) is a significant step towards an understanding of chemical cigarette biogenesis [43]. This new algal toxin related to C-CTX-1 was found in isolates of dinoflagellates collected in St. Thomas in the U. S. Virgin Islands, a geographical area at risk in the Caribbean Sea [43]. C-CTX-5 is likely to be half as potent as C-CTX-1 based on in vitro CBA-N2a. It was demonstrated that metabolization by liver microsomes of an omnivorous fish (sheepshead _Archosargus productcephalus_) at the C3 position produces C-CTX-1/-2 [43]. In addition, _G. silvae_ appears to be capable of producing low levels of C-CTX-1 (\(\sim\)7-8% of the level of C-CTX-5) [43]. Thus, _Gambierdiscus silvae_ and _Gambierdiscus exribaeus_ can be implicitly considered as algal producers of the Caribbean ciguatera food chain. To our knowledge, no analogue with [M+H]\({}^{+}\) at \(m/z\) 1139.6 has been reported in Atlantic fish. This research work [43] offers \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Name** & **C-CTX-1159** & **C-CTX-3/-4**[120] & **C-CTX-1157** & **C-CTX-1127** \\ \hline
[M+H]\({}^{+}\)\(m/z\) & 1159.6 & 1143.6 & 1157.6 & 1127.6 \\ \hline Polarity \({}^{\star}\) & + & & & \\ \hline Reported in Caribbean & [42; 108] & [23; 38; 41; 42; 108; 120] & [23; 38; 41; 42; 108] & [23; 41; 42] \\ \hline Reported in fish from & & & & \\ Macaronesia & [110] & [131] & [175; 176] & [113; 175] \\ \hline Potential toxicity & [108; 110] & [108] & [40; 108] & [175] \\ \hline \multirow{2}{*}{Putative structure} & Hydroylated C-CTX-1 & reduced C-CTX-1/-2 & \multirow{2}{*}{Oxdised C-CTX-1} & Loss of CH\({}_{2}\) or \\  & or oxidised C-CTX-1143 & hemiketals [120] & & demethylylated C-CTX-1 \\ \hline \hline \end{tabular}  
* in terms of polarity, C-CTX-1 is before C-CTX-1127.  
\end{table} 
Table 7: Caribbean ciguatoroxins analogues (C-CTXs) identified in fish from the Caribbean Sea and Macaronesia.