ciguatoxins and Body-Weight

Ciguatera fish poisoning is a seafood-toxin illness resulting from consumption of fish contaminated with ciguatoxins. Managing ciguatera fish poisoning is complex. It is made easier, however, by local fishers from endemic areas reporting regional predictability for local fish species' ciguatera fish poisoning risk, which the present study then tested. We investigated the prevalence of ciguatoxins in 4 commonly marketed and consumed species (Balistes vetula, Haemulon plumierii, Ocyurus chrysurus, and Epinephelus guttatus) across an oceanic gradient (north, south, east, and west) from the US Virgin Islands. Fish muscle extracts were analyzed for Caribbean ciguatoxins using an in vitro mouse neuroblastoma (N2a) cytotoxicity assay and confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fish collected from the north location had 0 fish with detectable ciguatoxins; this site also had the greatest wave energy. Caribbean ciguatoxins in fish ranged from 0.01 to 0.11, 0.004 to 0.10, and 0.005 to 0.18 ng Caribbean ciguatoxin-1 eq/g, from the west, east, and south respectively. Ciguatoxin-like activity was detectable by the N2a assay in 40, 41, 50, and 70% of H. plumierii, O. chrysurus, B. vetula, and E. guttatus, respectively. Of the fish collected, 4% had Caribbean ciguatoxin levels exceeding the US Food and Drug Administration guidance of 0.1 ng Caribbean ciguatoxin-1 eq/g fish. These findings concurred with spatial ciguatera fish poisoning prevalence information provided by local fishers in the US Virgin Islands and demonstrate how partnerships between researchers and fishers can aid the improvement of science-based ciguatera fish poisoning management. Environ Toxicol Chem 2018;39:1852-1863. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Topics: Animals; Body Size; Body Weight; Caribbean Region; Cell Line; Chromatography, Liquid; Ciguatoxins; Environmental Exposure; Mice; Muscles; Oceans and Seas; Perciformes; United States Virgin Islands

Ciguatoxins (CTXs) cause long-term disturbance of cerebral functions. The primary mechanism of neurotoxicity is related to their interaction with voltage-gated sodium channels. However, until now, the neurological targets for CTXs in the brain of intact animals have not been described. In our study, 1 day following oral exposure to 0.26 ng/g of Pacific ciguatoxin 1 (P-CTX-1), we performed in vivo electrophysiological recordings in the rat anterior cingulate cortex (ACC) and identified the increase in spontaneous firings and enhanced responses to visceral noxious stimulation. Local field recordings characterized the P-CTX-1-induced synaptic potentiation and blockage of the induction of electrical stimulation-induced long-term potentiation in the medial thalamus (MT)-ACC pathway. Furthermore, intracerebroventricular administration of P-CTX-1 at doses of 1.0, 5.0, and 10 nM produced a dose-dependent increase in ACC neuronal firings and MT-ACC synaptic transmission. Further studies showed upregulated Na(+) channel expression in astrocytes under pathological conditions. We hypothesized that the astrocytes might have been activated in the ciguatera poisoning in vivo. Increases in glial fibrillary acid protein expression were detected in reactive astrocytes in the rat ACC. The activation of astroglia was further indicated by activation of the gap junction protein connexin 43 and upregulation of excitatory amino acid transporter 2 expression suggesting that glutamate was normally rapidly cleared from the synaptic cleft during acute ciguatera poisoning. However, neurotoxicity and reactive astrogliosis were not detected in the ACC after 7 days of P-CTX-1 exposure. The present results are the first characterization of P-CTX-1-invoked brain cortex neuronal excitotoxicity in vivo and supported the theme that neuron and astroglia signals might play roles in acute ciguatera poisoning.

Topics: Action Potentials; Administration, Oral; Animals; Astrocytes; Body Weight; Ciguatera Poisoning; Ciguatoxins; Connexin 43; Convalescence; Dose-Response Relationship, Drug; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Transporter 2; Gliosis; Gyrus Cinguli; Injections, Intraperitoneal; Injections, Intraventricular; Long-Term Potentiation; Male; Microdialysis; Neurons; Random Allocation; Rats; Rats, Sprague-Dawley; Synaptic Transmission; Thalamus; Voltage-Gated Sodium Channels

Ciguatera is a common illness in tropical and subtropical regions that manifests in complex and long-lived symptoms which are more severe in subsequent exposures. This study measures central and peripheral neurologic signs, in parallel with blood toxin levels, in mice exposed once or twice (at 3 days interval) to a sublethal dose of ciguatoxin P-CTX-1 (0.26ng/g via i.p.). Mice were implanted with radiotransmitters to monitor motor activity and core temperature. A single exposure to ciguatoxin elicited an immediate and transient decrease in motor activity and temperature, and subsequent long-lasting thermoregulatory dysfunction resulting in stabilized body temperature around 36.0 degrees C with no observable circadian rhythm. The hypothermic response and the reduced activity were enhanced with a second exposure with 30% of the mice dying within 7h. Measurement of the peripheral nervous system by the tail flick assay revealed increased latency with a single ciguatoxin exposure, and a greater effect following the second exposure. Toxin was measurable in blood up to 3 days following the first exposure; at the 1h time point the concentrations were significantly elevated after a second exposure. These findings indicate an early response to ciguatoxin manifest in a central response to lower body temperature and reduce motor activity and a more persistent effect on the peripheral system leading to spinal heat antinociception and delayed fever-like response. The greater neurological response to a second ciguatoxin exposure was associated with elevated concentrations of ciguatoxin in the blood solely over the first hour of exposure. In conclusion, a single exposure to toxin exerts a significant neurological response which may be enhanced with subsequent exposure.

Topics: Animals; Body Temperature; Body Temperature Regulation; Body Weight; Cell Survival; Ciguatoxins; Male; Mice; Mice, Inbred C57BL; Motor Activity; Pain Measurement; Poisons

Topics: Animals; Body Temperature; Body Weight; Ciguatera Poisoning; Ciguatoxins; Disease Outbreaks; Dose-Response Relationship, Drug; Hong Kong; Humans; Mice

Ciguatera fish poisoning (CFP) has been a significant and increasing public health problem in Hong Kong since 1980s. With growing demand for imported live coral fishes, the number of people who suffered from this disease has also been increasing. An outbreak of CFP in 2004 was the second most prominent in record as compared with the most significant one that occurred in 1998. In 2004, out of a total of 823 reported food poisoning outbreaks involving 3159 persons, 65 incidents (7.9%) affecting 247 people (7.8%) were attributed to CFP. Validated mouse bioassay analysis of surveillance samples revealed that seven samples (13%) were confirmed to be contaminated with ciguatoxins (CTXs). Typical symptoms of CTXs were found in mice injected with 20mg of fish extracts. The causative fishes included Cheilinus undulatus, Epinephelus coioides, Plectropomus areolatus, and Plectropomus leopardus. Most of these CTX-positive samples analyzed had only trace amounts of CTXs in their extract, except a C. undulatus sample which contained a mice lethal dose (2.5MU/20mg ether extract). This fish species was also the major origin of coral fish that caused clusters of CFP in the last quarter of 2004. Cigua-Check analysis of 20 flesh grains from seven CTX-positive fishes, previously confirmed as CTX-positive samples by mouse bioassay, showed that 50% of flesh grains were CTX contaminated.

Topics: Animals; Biological Assay; Body Weight; Ciguatera Poisoning; Ciguatoxins; Disease Outbreaks; Female; Fishes; Food Contamination; Hong Kong; Humans; Meat; Mice; Mice, Inbred ICR

Mannitol (1 g/kg i.v.) is currently the treatment of choice for acute ciguatera, but confirmation of this treatment's apparent efficacy awaits further experimental or controlled clinical evidence. In mice, mannitol (1 g/kg i.v.) administered before or after i.p. ciguatoxin did not influence the signs of intoxication or the time to death. The effects of oral ciguatoxin differed from those following i.p. ciguatoxin, but again i.v. mannitol provided no detectable benefit. Development of hypothermia was rapid in mice receiving i.p. or oral ciguatoxin and was unaffected by i.v. mannitol. A sublethal i.p. dose of ciguatoxin initially retarded (day 0-4) but then accelerated (day 4-12) the growth of mice. Mannitol (i.v.) had no influence on these effects of ciguatoxin on the growth of mice. Ciguatoxin inhibited responses of isolated diaphragms to nerve stimulation (ED50 = 9 x 10(-11) M), while directly stimulated diaphragms were inhibited by five-fold higher concentrations. Mannitol (50 mM) added to the organ bath did not influence the ciguatoxin-induced inhibition of diaphragm responses to nerve stimulation in vitro. Responses of isolated diaphragm to nerve stimulation were normal in preparations removed from ciguatoxin-treated mice displaying pronounced dyspnoea (gasping). However, responses to nerve stimulation were reduced in preparations removed from mice immediately following death from ciguatoxin. Mannitol (i.v.) partially protected the phrenic nerve-diaphragm from this effect of ciguatoxin in vivo. We conclude that the lethal effects of ciguatoxin in mice probably stem from a central action, and suggest that species differences may account for the absence of any marked beneficial effect of i.v. mannitol in the mouse model for ciguatera in humans.

Topics: Animals; Body Weight; Ciguatera Poisoning; Ciguatoxins; Diaphragm; Disease Models, Animal; Female; Hypothermia; Lethal Dose 50; Male; Mannitol; Mice; Muscle Contraction; Phrenic Nerve

Epidemiologic characterization of ciguatera fish poisoning has been limited by lack of laboratory confirmation, absence of prospective follow-up, and incomplete analysis of age-related factors. A 1985 outbreak on the island of Kauai in the state of Hawaii that involved 15 persons of various ages was investigated to determine factors associated with disease severity. The presence of ciguatoxin was detected in leftover portions of the implicated fish by enzyme immunoassay. All cases were medically and epidemiologically investigated and followed prospectively. Ten of the 15 cases demonstrated bradycardia; seven were hospitalized, including two requiring placement in intensive care. Bradycardia was associated with increasing age and body weight (P < 0.01 and < 0.05, respectively) as well as the amount of toxic fish consumed (P < 0.01). Duration of illness ranged from two to 132 days. Increasing duration of illness was correlated with both increasing age and weight (rs = 0.64 and rs = 0.72, respectively, both P < 0.01) and was independent of amount and components of toxic fish consumed. The correlation between increasing age and weight with duration and severity of symptoms may be explained by prior subclinical toxin exposure and is consistent with the observation that repeated ciguatoxin exposures are associated with more severe illness. The association between amount of toxic fish consumed and bradycardia is consistent with an increased dose of ciguatoxin. The findings of this outbreak investigation support previously unconfirmed observations.

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Body Weight; Bradycardia; Child; Child, Preschool; Ciguatera Poisoning; Ciguatoxins; Cohort Studies; Disease Outbreaks; Eating; Female; Fishes; Food Analysis; Foodborne Diseases; Hawaii; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prospective Studies; Time Factors