ResearchPDF Available

Abstract and Figures

The review discusses the biotoxin named ciguatoxin. It discusses its structure, chemical properties, pharmacology effect, signs and symptoms and prevention and cure.
Content may be subject to copyright.
A REVIEW ON
CIGUATOXINS
Miriam Vuiyasawa (s11097959)
5-20-2016
Table of contents
1.0 Introduction
2.0 Structure and properties
3.0 Occurrence
4.0 Effect on mammals and marine organisms
5.0 Pharmacological effect
6.0 Signs and symptoms
7.0 Prevention and cure
8.0 Conclusion
9.0 Bibliography
1.0 Introduction
Ciguatoxin (CTX), although recorded throughout history through various food poisonings memoirs from
the early Tang Dynasty between 618-907 AD to Captain Cook and his crew on the HMS Resolution in
1774 off the coast of Vanuatu (Achaibar, et al., 2007), yet there is still little known and even less
understood about this biotoxin (Higa, et al., 2012). Ciguatoxin is a group of colorless, odorless, heat-
stable and lipid soluble compounds of which there is only knowledge of the existence of 41 types found
throughout the Atlantic, Caribbean and South Pacific waters (Darracq, 2014). Ciguatoxins are present in
carnivorous fish located in the mentioned areas and have similar chemical structures as breventoxins
(Hidalgo, et al., 2002) another biotoxin that also binds to the sodium voltage channel in the neurons.
The ciguatoxins which actually cause poisoning only become ciguatoxins due to biotransformation of
precursor compound known as gambiertoxins initially produced by the dinoflagellate Gambierdiscus
toxicus in the fish (European Food Safety Authority (EFSA), 2010), meaning that, the fish converts
biogambiertoxins into ciguatoxins. These dinoflagellates are commonly found in seaweeds, sands and
dead corals in which the small herbivorous fish feed on. As the bigger carnivorous fish feeds on the
herbivorous ones, ciguatoxins accumulates in them (Egmond, et al., 2004) resulting in Ciguatera Fish
Poison (CFP) when humans consume them. It is important to be aware of ciguatoxin as it is the most
common food-borne disease related to the consumption of finfish (Dickey & Plakas, 2010)and also no
reliable cure has been found. On a global scale, the collection of ciguatera has been insufficient as its
impact on the public health is overly underestimated as most do not report this illness, this indicates the
lack of conviction that anything can be done to cure the disease. In non-endemic regions,
underreporting appears to result from the lack of diagnostic recognition of ciguatera poisoning by
consumers and medical practitioners (McKee, et al., 2001.). Lewis and Sellin (1992) estimated that over
25,000 people worldwide are affected annually by ciguatera.
2.0 Structure and Properties
The structure of ciguatoxin (CTX) was discovered in 1967, when the toxin was successfully
isolated (Scheuer, Takahashi, Tsutsumi, & Yoshida, 1967) from moray eel (Scheuer, et al.,
1967;Tachibana, et al., 1987;Murata, et al., 1990). Ciguatoxins are lipid soluble polyether
compounds which consist of 13 to 14 linakegs into a rigid ladder-like structure. The structures
and characteristics of CTX differs in the Pacific (P-CTX), Carribean (C-CTX) and (I-CTX) the Indian
Ocean(Chan, 2014). The Pacific toxin has the greatest effect as an activator of voltage-sensitive
sodium channel in the membranes of nerves and muscles that are excitable (FAO, 2004;
Litaker, et al., 2010; Lewis, 2006). The three main pacific ciguatoxins known as the P-CTX-1, P-
CTX-2 and P-CTX-3 are even present in fish at different amounts(Egmond, Apeldoorn, Speijers,
& Nations, 2004). Modification of the structures are mostly seen at both the ends of the toxin
which is mostly through oxidation(Egmond, Apeldoorn, et al., 2004). The carribean (and indian)
toxin appears different from the pacific ciguatoxin as it is less polar, two of the structure of the
C-CTX were determined in 1998 identified as C-CTX-1 and C-CTX-2. There are several other
structures of ciguatoxins that have been identified however CTX-1 is discovered to be the main
toxin in carnivorous fish and also poses a human health threat at level above 0.1µg/kg
fish(Egmond, van Apeldoorn, Speijers, & Nations, 2004).
Ciguatoxins are relatively stable as they remain toxic after cooking, exposure to mild acidic and
basic conditions(Egmond, Apeldoorn, et al., 2004) and also a study in 2011 shows that the
toxins cannot also be removed even by freezing(Matte, Molgo, & Benoit, 2014).
Figure 1.0: The structure of ciguatoxin from G. toxicus and Mory eel liver. (Hokama & Yoshikawa-
Ebesu, 2001)
3.0 Occurrence
Ciguatoxins are naturally found in reef fishes that are in the tropical Caribbean, sub-tropical pacific and
the Indian ocean (Lehane & Lewis, 2000) and is mostly due to the presence of the dinoflagellate
Gambierdiscus toxicus which are observed to be distributed in these tropical regions(Lewis, 2001). The
reason for its preference to these waters is because they provide optimal conditions such as
temperature, salinity and light intensity (Bomber, Guillard, & Nelson, 1988) This dinoflagellate has been
observed to grow epiphytically with red, green and brown seaweeds corals (Egmond, van Apeldoorn, et
al., 2004) but some occur freely in sediments and dead corals. Although it was known that
Gambierdiscus toxicus leads to the production of ciguatoxin, nowadays this taxon is reported to have
genetically and morphological distinct groups. Studies have shown that ciguatoxins are now found in
other places globally.
Figure 1.0 Transmission path of ciguatera toxin from the marine dinoflagellate Gambierdiscus
toxicus through herbivorous and carnivorous fishes to man.
(Hokama & Yoshikawa-Ebesu, 2001)
In 2008, new species of the dinoflagellate Gambierdicus were discovered in the European Atlantic
waters and in the Mediterranean Sea(K & G, 2008), In addition CFP cases were also reported from Africa
and Europe including Madeira(Kim, 2013). A study was conducted from the year 1980 to 1983, to
determine the uptake and distribution of ciguatoxin in Caribbean fish in which lipids was extracted from
different parts of the fish and were analyzed using mouse bioassay. It was seen that the highest
concentration of ciguatoxin was found in the viscera, mostly in the liver, spleen and kidney with the
lowest concentration in the fish bones. In addition, it was also observed that the ratio of ciguatoxin
present in the viscera and the flesh of the fish varied with different species of the fish, thus it was
concluded that the toxin was distributed in differently in different fish. It was then gathered that blood
was involved in the dispersal of the toxin as the highly vascularized organs contained the highest
concentration of the toxin (De Fouw, et al., 1999;Pottier, et al., 2001) The expanding presence of the
ciguatoxin in the waters is due to the international trade of affected fish from the Pacific, Indian and the
Caribbean seas. As stated by the Robert Dickey; in 2007 alone the United States and the European Union
imported more that 80% of fishery product in order to meet the consumer need (Dickey & Plakas, 2010)
which caused CFP to be reported in the continental US. Resulting from the spread of CFP in the non-
endemic regions led worldwide public health institutions to rank ciguatera as the most common food-
borne disease relating to fin-fish consumption(De Fouw, Van Egmond, & Speijers, 1999).
4.0 Effect on Mammals and Marine Organisms
Ciguatoxin is responsible for the many symptoms shown when one has ciguatera poisoning and has also
been associated with many neurological ailments in humans. However, the effect of this toxin is not
limited to humans but affects other organisms both terrestrial and marine. According to Vasconcelos, et
al., 2010, due to reef fish being the target vector for ciguatoxins because of their probable resistance to
the toxin, there is not much known on the effects it has on the development and reproduction of marine
invertebrates as most studies concerning ciguatoxins revolve around vertebrates. For example, in a
study published by () male ICR mice were given a dose of ciguatoxin at 0.7µg/Kg of body weight and the
changes that occurred to the mice observed. They noticed ultrastructural changes in the organs such as
the heart, adrenal glands and the penis, however, much was learned from the research concerning heart
disease. For a period of 15 days the researchers induced the mice with a dose of 0.1 µg/Kg of body
weight of ciguatoxin on a daily basis and observed the morphological changes that occurred on the
heart. They found that in comparison with the large dose, the low dose showed no definitive
morphological change when administered once, however, with continual small dosages, growth of
collagen began in the interstitial spaces of the heart which continued for 14 months. This showed that
continual exposure to ciguatoxin could increase the chance of heart disease in mammals. In addition,
apart from the usual symptoms that affect humans, ciguatoxin has also been noted to be also present in
body fluids and can be transferred during intercourse or during pregnancy from the mother to the fetus
through the placenta as well as through breastmilk(Egmond, Apeldoorn, et al., 2004). In another study
conducted on mice and chicken exposed to lethal doses of ciguatoxins from fish in the Central Pacific,
both showed respiration impairment occurring first followed by cessation and hypotension. Conversely,
when exposed to non-lethal doses, irregular respiration occurred.
5.0 Pharmacological Effect
In earlier pharmacoloical studies of ciguatoxin, an experiment conducted using rabbit; it was
observed that the muscle contraction was greater when the blood was initially primed with CFP
before adding acetylcholine, blood with glucose (Egmond, Apeldoorn, et al., 2004) .Due to the
expanding knowledge of ciguatoxin chemistry, this data was found unrealible as the report was
given with no preparation of the CFP(). In 1972, a study was conducted with partially purified
ciguatoxin, it showed that the physiological effect of CFP was not due to an anticholisterase
action(K.M, 1965) however it activates the opening of the voltage-dependant sodium channel
in the cell membranes(Hokama & Yoshikawa-Ebesu, 2001). The toxin increases the sodium ion
transfer and thus the nerve cell depolarises, which is believed to cause the the neurological
signs associated with CFP (Seino, Kobayashi, Momose, Yasumoto, & Ohizumi, 1988).
Electrophysiological studies conducted with rats and humans affeted with CFP, obtained
indirect findings that ciguatoxins acts on the mammalian nerves by prolonging sodium channel
actions (Cameron, et al., 1991;Cameron, et al., 1991)
Also ciguatoxin is reported to affect the transport of calcium ions in the intestinal epithelial cell.
Ciguatoxins causes an increase in the concentration of calcium ions which acts as a second
messenger in the cell in which it discrupts the important ion-exchange system (Lehane & Lewis,
2000; Botana, 2014)
In lower doses of ciguatoxin both the respiratory and cardiovascular systems are affected.
Though ciguatoxin blocks neuromuscular properties, depression of the central respiratory
center is the main cause of the respiratory arrest caused by lethal doses of the toxin (T, et al.,
1987; K.M, 1965). However, in the cardio vascular system the effect has two phase in which
hypotensions occurs first with a slow heart action followed by hypertension with an abnormal
rapid heart rate (Li, 1965; Legrand, et al., 1982).
Other experimental studies of CTX extracts in animals included:
1. The accumulation of γ-aminobutyric acid and dopamine being inhibited (Vale, Antelo, &
Martín, 2015)
2. Frequency of depolarization increased (Friedman et al., 2008)
3. Cause of nodal swelling (Bidard J. N., Chungue, Legrand, Bagnis, & Lazocunski, 1984)
Earlier phamarcology studies conducted with crude ciguatoxins are questionable as they
include contaminating compunds(Cameron, Flowers, & Capra, 1991) which may add to the
proposed effect of ciguatoxin.
6.0 Ciguatoxins Signs and Symptoms
Ciguatera poisoning, a phenomenon documented many times throughout history has been recorded to
affect over 50,000 people globally every year. Some of the reasons ciguatera poisoning has become a
concern is because apart from this toxin being able to accumulate in the human body over time, there is
no immunity against it(Benoit, Juzans, Legrand, & J, 1996). Nevertheless it is rarely lethal. The symptoms
associated with ciguatera poisoning affect three main systems of the human body, namely the digestive,
cardiovascular and neurological systems. Certain symptoms related to the digestive system being
compromised by ciguatoxins include nausea, vomiting, abdominal cramps and diarrhea, all of which
develop within 6-24 hours of eating contaminated fish and typically last 1-3 days. In the case of the
cardiovascular system being affected, the following symptoms such as hypotension and bradycardia are
prevalent during the early stages of poisoning. In addition, paresthesia or the abnormal tinkling feeling
in the hand, feet, taste alteration, fatigue and an exaggerated hot and cold feeling have been linked to
ciguatera poisoning due to alterations in the charges in sodium gated channels thus causing cerebral
disturbances including slow motor neuron responses.
7.0 Prevention and Cure
In the case of ciguatera poisoning, there is no singular effective treatment or cure. This is due to the fact
that even though the symptoms show gastrointestinal and neurological surrender, the severity of the
poisoning showing only a single symptom at a time or a combination will depend on the geographical
location of the consumed fish as well as the type of fish eaten. In addition, there are no reliable human
biomarker to confirm that one is suffering from CFP and diagnosis is solely achieved by identifying the
symptoms and relating that information to the fish eating history of the patient. Even though this may
be a limitation to finding a suitable cure, extensive studies (Lehane & Lewis, 2000; Nicholson & Lewis,
2006; Bagnis, 1968; Calvert, et al., 1987) have been conducted on the symptoms and how to reduce its
effect on the human body and thus the current method and procedure of curing CFP can be trusted.
Studies conducted with gabapentin, an antiepileptic drug initially intended to imitate the function of
GABA in the central nervous system has been deemed effective in treating ciguatera poisoning as many
of the exaggerated neurological and physical symptoms deteriorated and eventually subsided upon
treatment according to one study. In addition, other drugs such as atropine sulphate and mannitol
have been found useful in lowering the severity of neurological symptoms and curing the ailment,
although the latter drug may not always be successful as was determined in the Cook Islands. According
to the study the effect of mannitol on those who suffered ciguatera poisoning in the Cook Islands was
the same as normal saline but with more side effects and a probable reason for this is the drastic
dependency on fish as a staple diet. However, with all the drugs in the world and all the studies
conducted in finding the absolute cure for this deadly toxin, the old mantra of prevention is better than
cure is one that must be adopted. Thus, educating populations on preventative measures that can be
undertaken, is vital. The best preventative action that can be taken is to avoid eating fish known to
cause ciguatera poisoning such as the moray eel, barracuda and snapper jack to name a few as well as
other fish from the same locality known to cause ciguatera poisoning. Nevertheless, this action cannot
be conducted unless there is primary education provided into differentiating the types of fish that cause
ciguatera poisoning as well as the regions in which they are found in. As seen in a study conducted by
(Friedman, et al., 2008) is a classic case of which patients with CFP were presented to 36 doctors in
South Florida; where CFP is endemic. From the diagnosis conducted, 68% of the doctors were able to
correctly diagnose CFP however only 47% of the physician were aware that CFP was a reportable
disease. Thus it can be said that most people, doctors included do not even know how to diagnose CFP,
making education on this issue all the more imperative.
8.0 Conclusion
The occurrence of ciguatera is seen to be increasing over the years due to increase in global
trade as well as the change the global environmental conditions causing the Gambierdiscus
taxon to invade other localities. Even though, ciguatoxins rarely affect marine invertebrates,
their ability to find the prefect vectors in the form of finfish shows how effective the
Gambierdiscus are at adapting to ecological changes. Though extensive research has been
conducted on ciguatoxins there has been no reliable cure found as many factors such as the
type of fish, geographical location of affected fish in addition the toxin itself has been found to
be heat-stable, and can also survive in acidic and basic conditions. As stated earlier, the lack of
report on CFP occurrence is a major limiting factor to the facilitating on further research to
discover a reliable cure. Thus, it is vital that awareness in educating the public is paramount in
preventing ciguatera fish poisoning.
Bibliography
Litaker, R. et al., 2010. Global Distribution of Ciguatera causing dinoflagellates in the genus
Gambierdiscus. Toxicon, Volume 56, pp. 711-730.
Achaibar, K. C., Moore, S. & Bain, P. G., 2007. Ciguatera poisoning. Practical Neurology, VII(5), pp. 316-
322.
Arnett, M. V. & Lim, J. T., 2007. Ciguatera Fish Poisoning: Impact for the Military Health Care Provider.
Military Medicine, CLXXII(9), pp. 1012-1015.
Bagnis, R., 1968. Clinical Aspect fo Ciguatera (fish poisoning) in French Polynesia. Hawaii Medical
Journal, XXVIII(1), pp. 25-28.
Bailey, S. & Withers, T., 2014. Ciguatera poisoning in the Cook Islands, London: BMJ Publishing Group
LTD.
Barton, E. D. et al., 1995. Ciguatera fish poisoning. A southern California epidemic.. Western Journal of
Medicine, CLXIII(1), pp. 31-35.
Benoit, E., Juzans, P., Legrand, A. M. & J, M., 1996. Nodal swelling produced by ciguatoxin-induced
selective activation of sodium channels in myelinated nerve fibers. Neuroscience, Volume 71, p. 1121
1131.
Bidard J. N., V. F. C. et al., 1984. Ciguatoxin is a novel type of Na+channel toxin. journal of Bioloy and
Chemistry, Volume 259, p. 83538537 .
Bomber, J. W., Guillard, R. R. L. & Nelson, W. G., 1988. Rôles of temperature, salinity, and light in
seasonality, growth, and toxicity of ciguatera-causing Gambierdiscus toxicus Adachi et Fukuyo
(Dinophyceae). Journal of Experimental Marine Biology and Ecology, 115(1), pp. 53-65.
Botana, L. M., 2014. Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection, Third
Edition. 3 ed. Boca Raton: CRC Press.
Calvert, G. M., Hryhorczuk, D. O. & Leikin, J. V., 1987. Treatment of Ciguatera Fish Poisoning with
Amitriptyline and Nifedipine. Jounal of Toxicology- Clinical Toxicology, XXV(5), pp. 43-48.
Cameron, J., Flowers, A. E. & Capra, M. F., 1991. Effects of ciguatoxin on nerve excitability in rats (part I.
J. Neurol. Sci. , Volume 101, p. 8792.
Cameron, J., Flowers, A. E. & Capra, M. F., 1991. Electrophysiological studies on ciguatera poisoning in
men (Part II). J. Neurol. Sci., Volume 101, p. 9397.
Caplan, C. E., 1998. Ciguatera fish poisoning. Canadian Medical Association. Journal, CLIX(11), p. 1394.
Chan, T. Y. K., 2014. Epidemiology and Clinical Features of Ciguatera Fish Poisoning in Hong Kong. Toxins,
Volume 6, pp. 2989-2997.
Darracq, M., 2014. Ciguatoxin A2 - Wexler, Philip. In: Encyclopedia of Toxicology (Third Edition). 3 ed.
Oxford: Academic Press, pp. 963-965.
De Fouw, J., Van Egmond, H. & Speijers, G., 1999. Ciguatera fish poisoning: a review, s.l.: NATIONAL
INSTITUTE OF PUBLIC HEALTH AND THE ENVIRONMENT.
Dickey, R. W. & Plakas, S. M., 2010. Ciguatera: A public health perspective. Toxicon, 52(2), pp. 123-136.
Donati, A. C., 2006. Ciguatera Poisoning. Fishnote, pp. 1-6.
Egmond, H. P., Apeldoorn, M. E. v., Speijers, G. J. A. & Nations, F. a. A. O. o. t. U., 2004. Marine Biotoxins.
s.l.:Food & Agriculture Org.
Egmond, H. P., van Apeldoorn, M. E., Speijers, G. J. A. & Nations, F. a. A. O. o. t. U., 2004. Marine
Biotoxins. Rome: Food and Agriculture Organization of the United Nations.
Egmond, H. P., van Apeldoorn, M. E., Speijers, G. J. A. & Nations, F. a. A. O. o. t. U., 2004. Marine
Biotoxins, Issue 80. 1 ed. Rome: Food & Agriculture Org..
FAO, 2004. Ciguatera fish poisoning In Marine Biotoxins, Rome: Food and Agriculture Organization of the
United Nations.
FARRELL, S. R., SARGOY, A., BRECHA, N. C. & BARNES, S., 2014. Modulation of voltage-gated Ca2+
channels in rat retinal ganglion cells by gabapentin. Visual Neuroscience, XXXI(1), pp. 47-55.
Friedman, M. A. et al., 2008. Ciguatera Fish Poisoning: Treatment, Prevention and Management. Marine
Drugs, pp. 456-479.
Higa, T. et al., 2012. Bioorganic Marine Chemistry, Volume 4. 4 ed. Berlin: Springer Science & Business
Media.
Hokama, Y., & Yoshikawa-Ebesu, J. S. M. (2001). CIGUATERA FISH POISONING: A FOODBORNE DISEASE.
Journal of Toxicology: Toxin Reviews, 20(2), 85-139. doi:10.1081/TXR-100105732
K.M, L., 1965. Ciguatera fish poison: a cholinesterase inhibitor. Science, Volume 147, pp. 1580-1581.
K, A. & G, N., 2008. Morphological identification of two tropical dinoflagellates of the genera
Gambierdiscus and Sinophysis in the Mediterranean Sea. Journal of Biological Research, Volume 9, pp.
75-82.
Kim, S., 2013. Marine Biomaterials: Characterization, Isolation and Applications. New York: CRC Press.
Lanio, M. E. et al., 2001. Purification and characterization of two hemolysins from Stichodactyla
helianthus. Toxicon, XXXVIV(2-3), pp. 187-194.
Legrand, A. M., Galonnier, M. & Bagnis, R. A., 1982. Studies on the mode of ciguatera toxins. Toxicon,
Volume 20, p. 311315.
Lehane, L. & Lewis, R., 2000. Ciguatera: recent advances but the risk remains. International Journal of
Food Microbiology, pp. 91-125.
Lehane, L. & Lewis, R. J., 2000. Ciguatera: recent advances but the risk remains. Internation Journal of
Food Microbiology, pp. 91-125.
Lewis, R., 2006. Ciguatera: Australian perspectives ona global problem. Toxicon, Volume 48, pp. 799-809.
Lewis, R. J., 2001. The Changing Face of Ciguatera. Toxicon, 39(1), pp. 97-106.
Li, K. M., 1965. A note on ciguatera fish poisoning and action of its proposed antidotes. Hwaii Medical
Journal, Volume 24, p. 358361.
Matte, C., Molgo, J. & Benoit, E., 2014. Involvement of both sodium influx and potassium efflux
inciguatoxin-induced nodal swelling of frog myelinated axons. Neuropharmacology, Volume 85, pp. 417-
426.
Murata, M. et al., 1990. Structures and configurations of ciguatoxin from the moray eel Gymnothorax
javanicus and its likely precursor from the dinoflagellate Gambierdiscus toxicus. Journal of the American
Chemical Society, 112(11), pp. 4380-4386.
Nicholson, G. M. & Lewis, R. J., 2006. Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion
Channel Function. Marine Drugs, pp. 82-118.
Perez, C. M., Vasquez, P. A. & Perret, C. F., 2001. Treatment of Ciguatera Poisoning with Gabapentin:
[Letter]. The New England Journal of Medicine, CCCXXXIV(9), pp. 692-693.
Pottier, I., Vernoux, J.-P. & Lewis, R. J., 2001. Ciguatera Fish Poisoning in the Caribbean Islands and
Western Atlantic. In: G. W. Ware, ed. Reviews of Environmental Contamination and Toxicology:
Continuation of Residue Reviews. New York: Springer New York, pp. 99-141.
Schep, L. J., Slaughter, R. J., Temple, W. A. & G Beasley, D. M., 2010. Ciguatera poisoning: an increasing
occurrence in New Zealand. The New Zealand Medical Journal (Online), CXXIII(1308), pp. 100-103.
Scheuer, P. J., Takahashi, W., Tsutsumi, J. & Yoshida, T., 1967. Ciguatoxin: Isolation and Chemical Nature.
Science, 155(3767), pp. 1267-1268.
Tachibana, K., Nukina, M., Joh, Y.-G. & Scheuer, P. J., 1987. Recent Developments in the Molecular
Structure of Ciguatoxin. Biological Bulletin, 172(1), pp. 122-127.
Thomas, I. K. & Hamilton, H. A., 1968. Marin Toxins from the Pacific-IV Pharmacology of Ciguatoxins.
Toxicon, VI(1), pp. 57-58.
T, M. J., K, K. C., K, S. L. & Y, H., 1987. The similarity of toxins. Ctenochaetus strigosus and cultured
Gambierdiscus toxicus.. Kent ridge: Faculty of Medicine, National Univ. of Singapore.
Vasconcelos, V., Azevedo, J., Silva, M. & Ramos, V., 2010. Effects of Marine Toxins on the Reproduction
and Early Stages Development of Aquatic Organisms. Marine Drugs, VIII(1), pp. 59-79.
Achaibar, K. C., Moore, S. & Bain, P. G., 2007. Ciguatera poisoning. Practical Neurology, VII(5), pp. 316-
322.
Arnett, M. V. & Lim, J. T., 2007. Ciguatera Fish Poisoning: Impact for the Military Health Care Provider.
Military Medicine, CLXXII(9), pp. 1012-1015.
Bagnis, R., 1968. Clinical Aspect fo Ciguatera (fish poisoning) in French Polynesia. Hawaii Medical
Journal, XXVIII(1), pp. 25-28.
Bailey, S. & Withers, T., 2014. Ciguatera poisoning in the Cook Islands, London: BMJ Publishing Group
LTD.
Barton, E. D. et al., 1995. Ciguatera fish poisoning. A southern California epidemic.. Western Journal of
Medicine, CLXIII(1), pp. 31-35.
Calvert, G. M., Hryhorczuk, D. O. & Leikin, J. V., 1987. Treatment of Ciguatera Fish Poisoning with
Amitriptyline and Nifedipine. Jounal of Toxicology- Clinical Toxicology, XXV(5), pp. 43-48.
Caplan, C. E., 1998. Ciguatera fish poisoning. Canadian Medical Association. Journal, CLIX(11), p. 1394.
Darracq, M., 2014. Ciguatoxin A2 - Wexler, Philip. In: Encyclopedia of Toxicology (Third Edition). 3 ed.
Oxford: Academic Press, pp. 963-965.
Donati, A. C., 2006. Ciguatera Poisoning. Fishnote, pp. 1-6.
Egmond, H. P., van Apeldoorn, M. E., Speijers, G. J. A. & Nations, F. a. A. O. o. t. U., 2004. Marine
Biotoxins, Issue 80. 1 ed. Rome: Food & Agriculture Org..
FARRELL, S. R., SARGOY, A., BRECHA, N. C. & BARNES, S., 2014. Modulation of voltage-gated Ca2+
channels in rat retinal ganglion cells by gabapentin. Visual Neuroscience, XXXI(1), pp. 47-55.
Friedman, M. A. et al., 2008. Ciguatera Fish Poisoning: Treatment, Prevention and Management. Marine
Drugs, pp. 456-479.
Higa, T. et al., 2012. Bioorganic Marine Chemistry, Volume 4. 4 ed. Berlin: Springer Science & Business
Media.
Lanio, M. E. et al., 2001. Purification and characterization of two hemolysins from Stichodactyla
helianthus. Toxicon, XXXVIV(2-3), pp. 187-194.
Lehane, L. & Lewis, R., 2000. Ciguatera: recent advances but the risk remains. International Journal of
Food Microbiology, pp. 91-125.
Nicholson, G. M. & Lewis, R. J., 2006. Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion
Channel Function. Marine Drugs, pp. 82-118.
Perez, C. M., Vasquez, P. A. & Perret, C. F., 2001. Treatment of Ciguatera Poisoning with Gabapentin:
[Letter]. The New England Journal of Medicine, CCCXXXIV(9), pp. 692-693.
Seino, A., Kobayashi, M., Momose, K., Yasumoto, T., & Ohizumi, Y. (1988). The mode of inotropic action
of ciguatoxin on guinea-pig cardiac muscle. British Journal of Pharmacology, 95(3), 876-882.
Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1854214/
Schep, L. J., Slaughter, R. J., Temple, W. A. & G Beasley, D. M., 2010. Ciguatera poisoning: an increasing
occurrence in New Zealand. The New Zealand Medical Journal (Online), CXXIII(1308), pp. 100-103.
Thomas, I. K. & Hamilton, H. A., 1968. Marin Toxins from the Pacific-IV Pharmacology of Ciguatoxins.
Toxicon, VI(1), pp. 57-58.
Vale, C., Antelo, Á., & Martín, V. (2015). Pharmacology of ciguatoxins Phycotoxins (pp. 23-48): John
Wiley & Sons, Ltd.
Vasconcelos, V., Azevedo, J., Silva, M. & Ramos, V., 2010. Effects of Marine Toxins on the Reproduction
and Early Stages Development of Aquatic Organisms. Marine Drugs, VIII(1), pp. 59-79.
ResearchGate has not been able to resolve any citations for this publication.
Article
Full-text available
In the present review, the main objective was to describe the epidemiology and clinical features of ciguatera fish poisoning in Hong Kong. From 1989 to 2008, the annual incidence of ciguatera varied between 3.3 and 64.9 (median 10.2) per million people. The groupers have replaced the snappers as the most important cause of ciguatera. Pacific-ciguatoxins (CTX) are most commonly present in reef fish samples implicated in ciguatera outbreaks. In affected subjects, the gastrointestinal symptoms often subside within days, whereas the neurological symptoms can persist for weeks or even months. Bradycardia and hypotension, which can be life-threatening, are common. Treatment of ciguatera is primarily supportive and symptomatic. Intravenous mannitol (1 g/kg) has also been suggested. To prevent ciguatera outbreaks, the public should be educated to avoid eating large coral reef fishes, especially the CTX-rich parts. A Code of Practice on Import and Sale of Live Marine Fish for Human Consumption for Prevention and Control of Ciguatera Fish Poisoning was introduced from 2004 to 2013. The Food Safety Ordinance with a tracing mechanism came into full effect in February 2012. The Government would be able to trace the sources of the fishes more effectively and take prompt action when dealing with ciguatera incidents.
Article
Full-text available
Crystalline ciguatoxin isolated from moray eel (Lycodontis = Gymnothoraxja vanicus) viscera has an LDso of 0.45 g/kg (i.p., mice). It has a molecular weight of 1111.7 ± 0.2 daltons. 1HNMR studies have shown that it is a polar and highly oxy genated molecule belonging to the class of polyethers. On basic alumina ciguatoxin is reversibly converted to a chromatographically distinct less polar form, which is equally toxic and elicits typical ciguatoxin symptoms in mice. From parrotlIsh (Scarus sordidus), which originated on a ciguateric reef on Ta rawa atoll (Kiribati), we have isolated two toxins that evoke ciguatera symptoms in mice at approximately equal levels. Chromatographic evidence suggests that the two toxins are identical with the two ciguatoxins of different polarity and that the less polar form is the previously described scaritoxin.
Article
Full-text available
This case report presents two British medical students who contracted ciguatera poisoning while on elective in the Cook Islands. Thirty-six hours after consuming two reef fish they developed paraesthesia of the mouth, hands and feet, myalgia, pruritis and cold allodynia. Neurological examination was normal. Diagnosis of ciguatera poisoning was made on history of reef fish consumption and classical clinical presentation. Management was symptomatic (antihistamines) and both students made a full recovery within 10 weeks.
Article
Full-text available
The α 2 δ auxiliary subunits of voltage-gated Ca2+ channels (VGCCs) are important modulators of VGCC function. Gabapentin interacts with α 2 δ 1 and α 2 δ 2 subunits and is reported to reduce Ca2+ channel current amplitude (I Ca). This study aimed to determine the effects of gabapentin on VGCCs in retinal ganglion cells (RGCs). Whole cell patch clamp was used to record I Ca in isolated RGCs, and calcium imaging was used to measure Ca2+ transients from RGCs in situ. Immunohistochemistry was used to detect the presence of α 2 δ 1-containing VGCCs in isolated RGCs in the absence and presence of gabapentin pretreatment. Acute administration of gabapentin reduced I Ca and Ca2+ transients compared to control conditions. In isolated RGCs, pretreatment with gabapentin (4-18 h) reduced I Ca, and cell surface α 2 δ 1 staining was reduced compared to nonpretreated cells. Acute administration of gabapentin to isolated RGCs that had been pretreated further reduced I Ca. These results show that gabapentin has both short-term and long-term mechanisms to reduce I Ca in isolated RGCs. Some Ca2+ channel blockers have been shown to protect RGCs in retinal trauma suggesting that modulation of VGCCs by gabapentin may prevent the deleterious effects of elevated Ca2+ levels in RGCs in trauma and disease.
Book
The occurrence of marine and freshwater toxins is a rapidly evolving problem due to ever-changing circumstances. Expanding international commerce is forcing cargo ships into virgin territory, deforestation and pollution violate the natural ecological balance, and a changing climate holds unknown potential to alter current factors and trigger toxic blooms in new forms, at new rates, and in new places. Fortunately, with notable advances in analysis technology, the body of knowledge in the field is equally dynamic. In just six years since the first edition, toxins that warranted only line listings, including pfiestra, gambierol, and polycavernoside, are now worthy of entire chapters, requiring a new edition to encompass the expanding scope of the field. Emphasizes Human Response to New Toxins Gathering contributions from international experts, Seafood and Freshwater Toxins: Pharmacology, Physiology, and Detection, Second Edition provides an overview of the current state-of-knowledge from several perspectives. Incorporating toxicology, chemistry, ecology, and economics, the book covers the biological aspects of the bloom and the effects and actions of each toxin with emphasis on human response. This edition includes more information on detection and analysis, toxicological information on previously little known toxins, and food safety issues. Incorporating Pharmacological, Legal, and Economic Aspects, this book– • Begins with general information on risk assessment and analytical techniques • Cover several categories of toxins by function and biomechanism • Considers potential pharmacological applications and the use of toxins as precursors to therapeutic drugs • Highlights the legal and economic perspectives of toxic incidence in industrial activity and international regulation and monitoring programs • Describes new toxins by their individual chemical structure, ecobiology, metabolism, detection methods, determination, pharmacology, and toxicology.
Article
The ciguatera-causing dinoflagellate Gambierdiscus toxicus Adachi et Fukuyo reached maximum abundance in the Florida Keys when the water temperature was ≈ 30°C; populations were over half maximum when temperature lay in the interval 27–30°C. In laboratory unialgal culture experiments, temperatures >29 and <26°C limited division rates, although growth was possible from 19.5 to 34°C. Optimum growth occurred at 32%, salinity, division rates at 25 and 40%, were only 34 and 57% of maximum, respectively. Fastest division rates in light-quality experiments were achieved under blue-violet to blue light (435 and 465 nm) with gamma slopes (light-limited growth rate increases) of 0.54 and 0.42, respectively. The gamma slope under green light (525 nm) was 0.36. Growth under fluorescent light was reduced >1.4 × 1016 quanta.cm-2 · s-1 (≈ 11% of full sunlight). Under optimum combinations of the aformentioned parameters, growth rates > 0.5 division · day-14 could be sustained and led to unusually high yields in large scale cultures of up to 360 mg (dry weight) · 1-1. Cultures grown at 27°C were more toxic than those at 21°C (3515 ± 500 cells · MU-1 vs. 16536 ± 2400 cells · MU-1, sd). Cultures were also still capable of producing toxins at inhibiting high irradiance levels.
Article
This review is an extensive up-to-date compilation of ciguatera fish poisoning, a food borne disease, which covers all aspects of the problem, with the exception of clinical and therapeutic information. Thus brief accounts of the history, biology, chemistry, pharmacology, epidemiology, detection methods, pathology, and comprehensive references are presented.