Biomedical subjects
Publications and source records attributed to R Bagnis.
We propose a significant relationship between bursts of ciguatera following disturbance on a reef area and seepages of endo-upwelled interstitial waters, rich in nutrients. Such waters cannot continue to be used by a stressed or eliminated algal-coral ecosystem and are taken up by epibenthic planktons i.e. Gambierdiscus toxicus, of which population increases sharply.
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An epidemiological study on ciguatera fish poisoning in the French West Indies (St-Barthelemy, St-Martin and Anguilla) was conducted during the years 1985-1986. The investigation on intoxications shows a non seasonal significant prevalence. Though it was difficult to list the cases, the morbidity seems to vary between 7 and 30 per thousand. A study of fish toxicity was realised; 46 different species were tested (individually or by pools) by the mosquito bio-test. Observations of intoxications give the following results: High risk species: Caranx bartholomaei, C. lugubris, Seriola dumerili, Lutjanus apodus, L. jocu, Pristipomoides macrophtalmus, Gymnothorax funebris, G. moringa, Scomberomorus cavalla, S. regalis, Mycteroperca venenosa, M. tigris, Epinephelus morio, Sphyraena barracuda. Intermediate species: Caranx latus, C. ruber, Lachnolaimus maximus, Lutjanus analis, L. buccanella, L. griseus, Malacanthus plumieri, Scomberomorus maculatus. Low risk species: Balistes vetula, Alectis ciliaris, Haemulon album, Bodianus rufus, Halichoeres radiatus, Priacanthus arenatus, Alphestes afer. Many species are involved in the toxic food chain. New ones have been identified, but it is difficult to determine the toxic level range. A cartography is presented but no place is free of risk. A research of Gambierdiscus toxicus, the causal agent, on algal surface from dead corals was conducted around St-Barthelemy and St-Martin. The dinoflagellate is found in low or medium populations all around the islands with no difference between North and South. There is a maximal activity during the spring. A model of the epidemiology of the ciguatera in the area is proposed.
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Purified ciguatoxin at 0.1 to 10 ng/ml inhibits the net accumulation of neurotransmitters (gamma-aminobutyric acid and dopamine) by brain synaptosomes. This action is due to a stimulation of neurotransmitter release. The half-maximum effect of the toxin is observed at 0.62 ng/ml. The effect of ciguatoxin is completely inhibited by tetrodotoxin (K0.5 = 4 nM). Electrophysiological studies on neuroblastoma cells indicate that ciguatoxin induces a membrane depolarization which is prevented by tetrodotoxin and which is due to an action that increases Na+ permeability. Under appropriate conditions ciguatoxin creates spontaneous oscillations in the membrane polarization level and repeated action potentials. Ciguatoxin stimulates 22Na+ entry through the voltage-dependent Na+ channels of neuroblastoma cells and rat skeletal myoblasts when it is used in synergy with veratridine, batrachotoxin, pyrethroids, sea anemone, or scorpion toxins. The half-maximum effect of ciguatoxin on 22Na+ flux in the presence of veratridine occurs at a concentration of 0.5 ng/ml. Stimulation of 22Na+ flux by ciguatoxin is abolished by tetrodotoxin. These results taken together indicate that ciguatoxin belongs to a new class of toxins acting on Na+ channels.
Ciguatoxin and maitotoxin, extracted from a species of moray-eel, Gymnothorax javanicus, and from a wild dinoflagellate, Gambierdiscus toxicus, were tested on rat atria and rabbit duodenum. Biphasic inotropic and chronotropic responses with excitatory and inhibitory components were observed. The effects of agents such as reserpine, propranolol, phentolamine, atropine and manganese ions were investigated. We conclude that, at the dosage levels used, ciguatoxin acts mainly at the nerve endings, while maitotoxin exerts prominent toxic effects on muscles.
A rapid procedure for extraction and partial purification of ciguatoxin has been achieved and compared to one of the routine methods. Fish from two species which provided extracts of differing purity by the routine method were used. From 8 g of raw flesh, 1.0 +/- 0.2 mg of a semi-purified extract of ciguatoxin of homogeneous quality was obtained within 1 hr, whatever the species or toxicity of the fish. The results were reproducible, making the procedure very promising.
A new animal assay to detect ciguatoxin in fishes was developed. Mosquitoes were subjected to intrathoracic injection of serial dilutions of ciguatoxin crude extracts. Toxicity of the fishes was expressed as the mosquito LD50 (g of flesh per mosquito). A significant correlation between the mosquito bioassay and the mouse bioassay performed on the same extracts was shown (r = 0.72, n = 80). We were able to detect 96% of the toxic fishes, while 91% of the fishes non-toxic in mice were also non-toxic in mosquitoes.
Maitotoxin is a substance extracted from a dinoflagellate and certain tropical poisonous fish. It is considered as the most potent marine toxin (50 times more potent than tetrodotoxin). In isolated mammalian atria, maitotoxin produces at low doses a positive inotropic effect not modified by reserpine pretreatment and suppressed by Mn2+ ions. In the anaesthetized cat, it induces cardiac arrhythmias and tachycardia leading to cardiac failure. On the other hand, maitotoxin strongly inhibits Na+-K+ ATP-ase from microsomes of cat and human kidneys. In a rat pheochromocytoma cell line, it has been shown to promote a norepinephrine release and an increase in Ca2+ influx. The purpose of this work is to study the effect of maitotoxin on action potential of isolated perfused rat heart to check the existence of a direct effect on the myocardium.
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The effects of ciguatoxin, scaritoxin and maitotoxin, the main toxins involved in ciguatera fish poisoning, has been studied in pentobarbital anaesthetized cats. Intravenous injections of increasing doses of these toxins (5 to 160 microgram/kg of partially purified samples) evoked respiratory and cardiovascular disturbances: hyperventilation at low doses and respiratory depression leading to respiratory arrest at high doses; bradycardia and troubles of the atrioventricular conduction at low doses, arrhythmias and ventricular tachycardia with transient hypertension at sublethal doses, and falling arterial pressure leading to complete heart failure at high doses. The mode of action of ciguatoxin has been studied by testing the preventive effects of pharmacological compounds such as hexamethonium, atropine, propranolol and phentolamine and by proceeding to bilateral adrenalectomy. The results have indicated both central and peripheral effects. Cholinergic and also alpha-adrenergic actions were pointed out.
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Clinical observations on ciguatera were collected between 1964 and 1977 on 3,009 patients from several South Pacific island groups. Patients generally presented with neurologic symptoms such as parasthesia, vertigo, and ataxia, in addition to gastrointestinal symptoms such as diarrhea, abdominal pain, nausea, and vomiting. Patients with this illness usually became symptomatic less than 24 hours after ingestion of the fish and most patients (76.8%) developed symptoms in less than 12 hours. Significant differences in certain symptoms were noted between Melanesian and Polynesian ethnic groups, suggesting a susceptibility difference, or a difference in the nature of the toxin found in different areas of the Pacific. Being poisoned multiple times appeared to result in a clinically more severe illness than disease observed in patients experiencing ciguatera for the first time.
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Clinical and epidemiological observations suggested that a complex toxic molecule is involved in the parrotfish flesh (Scarus gibbus) poisoning from Gambier Islands. The fat soluble extract obtained from the muscles upon ciguatoxin preparation showed two toxic substances after fractionation by DEAE cellulose column chromatography. The major toxin is different from ciguatoxin judging by its chromatographic behaviour. The other is closely similar to (or identical with) ciguatoxin from the moray eel Gymnothorax javanicus. They were named SG1 for the new toxin and SG2 for the ciguatoxin like compound. Successive filtrations on Sephadex LH-20 of SG1 and SG2 gave respectively a lethality to mice of 0.03 microgram/g and 0.06 microgram/g. SG1, specifically occurs in the muscles of the parrotfish family (scaritoxin) while it is absent from other ciguateric fishes. According to that specificity and the lack of SG1 in S. gibbus liver and gut contents, the origin of scaritoxin is briefly discussed.
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A modification of the extraction procedure for obtaining ciguatoxic substances from the tissues of various poisonous reef fish has been developed. Rapid alkali treatment of the residue obtained at an early stage is efficient in separating the ciguatoxic fraction from toxic impurities which interfere with pharmacological tests. It is thus possibles to carry out a more precise dosage of the material separated in this way. Alkali treatment does not affect either the physiological activity in cats and mice of the ciguatoxic substances nor their behaviour in a preparative thin layer chromatography in a benzene-butanol system.
Two fractions of ciguatoxic extracts were isolated by chromatography. The first showed anticholinesterasic properties, while the other acted directly on the muscular fibre. These findings were histoenzymologically confirmed. Controls with non-toxic extracts of fishes from the coral benthos reinforce the theory of the ecological origins of ciguatoxins.