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Review

The Incidence of Tetrodotoxin and Its Analogs in the Indian Ocean and the Red Sea

by
Isidro José Tamele
1,2,3,
Marisa Silva
1,4 and
Vitor Vasconcelos
1,4,*
1
CIIMAR/CIMAR—Interdisciplinary Center of Marine and Environmental Research, University of Porto, Terminal de Cruzeiros do Porto, Avenida General Norton de Matos, 4450-238 Matosinhos, Portugal
2
Institute of Biomedical Science Abel Salazar, University of Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
3
Faculty of Sciences, Eduardo Mondlane University, Av. Julius Nyerere, nr 3453, Campus Principal, 257 Maputo, Mozambique
4
Department of Biology, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4619-007 Porto, Portugal
*
Author to whom correspondence should be addressed.
Mar. Drugs 2019, 17(1), 28; https://doi.org/10.3390/md17010028
Submission received: 28 November 2018 / Revised: 28 December 2018 / Accepted: 29 December 2018 / Published: 5 January 2019
(This article belongs to the Special Issue Marine Bacterial Toxins)
Browse Figure
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Abstract

:
Tetrodotoxin (TTX) is a potent marine neurotoxin with bacterial origin. To date, around 28 analogs of TTX are known, but only 12 were detected in marine organisms, namely TTX, 11-oxoTTX, 11-deoxyTTX, 11-norTTX-6(R)-ol, 11-norTTX-6(S)-ol, 4-epiTTX, 4,9-anhydroTTX, 5,6,11-trideoxyTTX, 4-CysTTX, 5-deoxyTTX, 5,11-dideoxyTTX, and 6,11-dideoxyTTX. TTX and its derivatives are involved in many cases of seafood poisoning in many parts of the world due to their occurrence in different marine species of human consumption such as fish, gastropods, and bivalves. Currently, this neurotoxin group is not monitored in many parts of the world including in the Indian Ocean area, even with reported outbreaks of seafood poisoning involving puffer fish, which is one of the principal TTX vectors know since Egyptian times. Thus, the main objective of this review was to assess the incidence of TTXs in seafood and associated seafood poisonings in the Indian Ocean and the Red Sea. Most reported data in this geographical area are associated with seafood poisoning caused by different species of puffer fish through the recognition of TTX poisoning symptoms and not by TTX detection techniques. This scenario shows the need of data regarding TTX prevalence, geographical distribution, and its vectors in this area to better assess human health risk and build effective monitoring programs to protect the health of consumers in Indian Ocean area.

1. Introduction

The tropical and subtropical climates predominant in the Indian Ocean zone, accompanied by industrialization and population increase, are pointed to as the main factors that, together with eutrophication, contribute to the development of toxic phytoplankton blooms—harmful algal blooms (HABs) and bacteria [1]. HABs and some bacteria are marine toxin (MT) producers, turning the Indian Ocean zone vulnerable to this phenomenon [2,3,4,5]. One of the main Indian Ocean MTs is tetrodotoxin (a neurotoxin) and its analogs (TTXs), of which the main producers were reported to belong to different bacteria genera [6,7,8,9,10,11,12,13,14,15]. Cases of human poisoning are recurrent, especially after consumption of TTX-contaminated fish, with the puffer fish as the most common vector reported since Egyptian times [16,17,18,19,20,21,22,23,24,25,26,27,28,29]. Due to the lack of TTX monitoring programs, the episodes of human seafood poisoning are still common in the Indian Ocean area, since seafood is the most common food for many people living along coastal zones [16,17,18,19,20,21,22,24,26,28,29,30,31,32,33,34,35,36,37,38]. Thus, the objective of this paper was to review the incidence of TTX in the Indian Ocean and the Red Sea zones and associated human seafood poisoning incidents. The monitoring of TTXs in this geographic zone is also recommended.

2. Tetrodotoxin

TTX (Figure 1) is a potent neurotoxin group [39] that can provoke severe poisoning after consumption of contaminated seafood. Several species of distinct marine organisms of human consumption were identified as TTX vectors: puffer fish [16,17,18,19,20,21,22,23,24,25,26,27,28,29], gastropods [40], crustaceans [41,42,43,44], and bivalves [45]. Also, the occurrence of TTXs in terrestrial vertebrates such as Polypedates sp., Atelopus sp., Taricha granulosa, [46] and Cynops ensicauda popei [47] was reported [48,49]. TTX is an alkaloid isolated for the first time in 1909 by Tahara and Hirata from the ovaries of globefish [50]. In the marine environment, bacteria are pointed to as the main producers of this group of toxins, namely Serratia marcescens [51], Vibrio alginolyticus, V. parahaemolyticus, Aeromonas sp. [52], Microbacterium arabinogalactanolyticum [13], Pseudomonas sp. [14], Shewanella putrefaciens [6], Alteromonas sp. [8], Pseudoalteromonas sp. [10], and Nocardiopsis dassonvillei [12]. Physicochemically, TTXs are colorless, crystalline weak heterocyclic basic compounds (Figure 1 and Table 1), highly hydro-soluble and also heat-stable [45]; thus, the toxin is not destroyed by cooking procedures.
To date, around 28 analogs of TTX were described (Figure 1 and Table 1) and some of them were detected in marine organisms [53], with their relative toxicity well known [45] (chemical structures pointed with asterisks in Figure 1): TTX, 11-oxoTTX, 11-deoxyTTX, 11-norTTX-6(R)-ol, 11-norTTX-6(S)-ol, 4-epiTTX, 4,9-anhydroTTX, 5,6,11-trideoxyTTX [45], 4-CysTTX, 5-deoxyTTX, 5,11-dideoxyTTX, and 6,11-dideoxyTTX [54,55,56,57] (Table 1). Their relative toxicity ranges from 0.01 to 1.0, with 5,6,11-trideoxyTTX and TTX as the least and most toxic, respectively [45], and there are still no available data regarding the toxicity for 4-CysTTX and 5,11-dideoxyTTX. Chemical abstract numbers (CAS) are also listed in Table 2.
The action mechanism of TTXs occurs through the occlusion of the external pore of site 1 of voltage-gated sodium channels on the surface of nerve membranes, blocking cellular communication and causing death by cardio-respiratory paralysis [60]. Paralysis occurs by affecting the respiratory system, the diaphragm, skeletal muscles, and tissues in the digestive tract in humans [39]. TTXs normally accumulate in skin, intestines, liver, muscle, gonads, viscera, and ovaries in different species of puffer fish [16,21,22,29,33,34,35,36,37,61,62,63,64,65]. The symptoms that can be used partially as an indication of TTX human poisoning (wt = 50 kg and TTX amount = 2 mg) were grouped into four levels depending on the amount ingested [66] and are described in Table 3. These symptoms normally appear 40 min after consumption of contaminated food and, in some cases, even six hours after [67].
Currently, there is no antidote for TTX; however, some studies indicate that the application of activated charcoal could help in reversing the clinical stage of poisoning victims since it reduces the toxin free amount [68]. Also, alkaline gastric lavage with sodium bicarbonate (2%) is indicated as a treatment within the first hour of the incident, due to TTX instability in alkaline media [69]. Another clinical intervention recommendation is the use of cholinesterase inhibitors such as neostigmine [28], and mechanical respiratory help may reduce mortality probability by muscle paralysis [38].

3. TTX Detection Methods

Several methodologies were developed to analyze TTXs and, in recent years, chemical methods became more popular due to their sensitivity with limits of detection (LODs) ranging from 0.9 ng to 0.063 μg. Liquid chromatography with tandem mass spectrometry (LC–MS/MS) techniques, the first choice compared to mouse bioassays (MBAs) and enzymatic methods due to their greater sensitivity and specificity, have the capacity to detect and determine TTXs in complex matrices [70]. Also, due to ethical reasons and lack of specificity, MBA fell into disuse, with the latter reason also attributed to the enzymatic methods. When a poisoning case occurs, it is recommended, when available, to screen the liver, muscle, skin, gonads, and ovaries of the suspected poisoning marine vector samples [28,36,40,41,42,53,54,55,56,62,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88]. Human urine and plasma should also be analyzed for TTX in these cases [80].
Methods for TTX analysis and their respective limits of quantification (LOQs) and detection (LODs) are described in Table 4 and include the mouse bioassay [12,36,52,89], receptor-based assay [90], immunoassay [31,36,52,73,77,82,89,91,92,93], thin-layer chromatography [13,72], high-performance liquid chromatography [84,94,95], gas chromatography–mass spectrometry [76,84,95], liquid chromatography coupled to mass spectrometry [33,40,96,97,98], surface plasmon resonance [30], and liquid chromatography with fluorescence detection (FLD) [15,32,89].

4. Geographic Occurrence and Incidence of TTXs in the Indian Ocean and the Red Sea

As described in the introduction section, TTXs were reported in several marine organisms [71], regarding poisoning incidents [71]; the main TTX vectors involved in the Indian Ocean and the Red Sea (Table 4) belong to the Tetraodontidae family: Arothron hispidus in India [65], Takifugu oblongus in Bangladesh [16,33] and India [35,62], Lageocephalus scitalleratus in Singapure [20], Pleuranacanthus sceleratus in Egypt [21,34,37], Reunion Island [29], and Australia [23,24], Chelonodon pataca, Sphaeroides oblongus, Lagocephalus inermis, and Lagocephalus lunaris in India [35,62], Xenopterus naritus in Malaysia [63], Arothron stellatus in India [64], Tetractenos hamiltoni in Australia [80,100], and Tetroadon sp. [17], Tetraodon nigroviridis, and Arothron reticularis in Thailand [99]. The records of TTX occurrence in other marine species such as mollusks are scarce in the Indian Ocean. Gastropods were reported as TTX vectors in other locations: Charonia lampas [85], Gibbula umbilicalis, and Monodonta lineata on the Portuguese coast [40], Nassarius spp. in China [94], Polinices didyma, Natica lineata [84,101], Oliva miniacea, O. mustelina, and O. nirasei [95] in Taiwan, Charonia sauliae [102], Babylonia japonica [86], Niotha spp. [75,81], and Tutufa lissostoma [103] in Japanese crabs, Demania cultripes, Demania toxica, Demania reynaudi, Lophozozymus incises, Lophozozymus pictor, Atergatis floridus [104], and Atergatopsis germaini [83], highlightinh these organisms as potential indicator species [11]. Data on these groups are scarce in the Indian Ocean area, suggesting that further studies and monitoring programs for TTXs are needed. Available data regarding this geographic region are displayed in Table 5.

5. Final Considerations

TTX data in the Indian Ocean and Red Sea are usually related to fatal outbreaks due to seafood poisoning and not to scientific research, indicating the lack of MT monitoring programs. The symptomatology reports and MBA are used to identify seafood poisoning caused by TTX and analogs, indicating the need for analytical methods such as liquid chromatography to obtain better quantitative data. Both symptomatology and MBA in isolation are not enough to conclude that TTXs are the causative agent of seafood poisoning, since there are other toxins (PSTs) with similar action mechanism that overlap in symptomatology with TTX poisoning. Additionally, MBA cannot discriminate between the different TTX analogs. MBA and symptomatology are used in countries of the Indian Ocean and the Red Sea to identify TTX poisoning due to the lack of availability and accessibility to chemical methods and the absence of TTX monitoring programs.
Thus, the implementation of monitoring programs using chemical analytical methods such as LC–MS/MS instead of MBA in the Indian Ocean and the Red Sea is urgently needed in different species of shellfish and puffer fish, including Arothron hispidus, Takifugu oblongus, Lageocephalus scitalleratus, Pleuranacanthus sceleratus, Chelonodon patoca, Sphaeroides oblongus, Lagocephalus inermis, Lagocephalus lunaris, Xenopterus naritus, Arothron stellatus, Tetractenos hamiltoni, Tetraodon nigroviridis, Arothron reticularisand, Charonia sauliae, Babylonia japonica, Niotha spp., and Tutufa lissostoma, since they are most consumed and are already confirmed to be vectors of TTX in the Indian Ocean and the Red Sea. These species can be used as indicators for monitoring programs using the maximum limit permitted of 2 mg·kg−1 (from Japan).

Author Contributions

V.V. and M.S. conceived the idea. I.J.T. drafted the manuscript. The final version of the manuscript was approved by all authors.

Funding

This research was partially supported by the framework of the Atlantic Interreg project ALERTOXNET—Network for introduction of Innovative Toxicity Alert Systems for safer seafood products—EAPA_317/2016.

Acknowledgments

We acknowledge the project H2020 RISE project EMERTOX—Emergent Marine Toxins in the North Atlantic and Mediterranean: New Approaches to Assess their Occurrence and Future Scenarios in the Framework of Global Environmental Changes—Grant Agreement No. 778069.

Conflicts of Interest

The authors declare no conflicts of interest.

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Marinedrugs 17 00028 g001 550
Figure 1. Tetrodotoxin (TTX) and analogs modified from European Food Safety Authority (EFSA) 2017 [45] and Yotsu-Yamasshita et al. (2007) [15,53,54]. (*) indicates TTX analogs that occur in marine organisms with known relative toxicity. (A) 4-cysTTX(*), (B) tetrodonic acid, (C) 4,9-anhydroTTX(*), (D) 1-hydroxy-5,11-dideoxyTTX, (E) TTX and 12 analogs, (F) 5-deoxyTTX(*) and three analogs, (G) trideoxyTTX and two analogs, (H) 4-epi-5,6,11-trideoxyTTX and another analog, and (I) 4,4a-anhydro-5,6,11-trideoxyTTX and 1-hydroy-4,4a-anhydro-8-epi-5,5,11-trideooxyTTX (see radicals of the analogs in the Table 1).
Figure 1. Tetrodotoxin (TTX) and analogs modified from European Food Safety Authority (EFSA) 2017 [45] and Yotsu-Yamasshita et al. (2007) [15,53,54]. (*) indicates TTX analogs that occur in marine organisms with known relative toxicity. (A) 4-cysTTX(*), (B) tetrodonic acid, (C) 4,9-anhydroTTX(*), (D) 1-hydroxy-5,11-dideoxyTTX, (E) TTX and 12 analogs, (F) 5-deoxyTTX(*) and three analogs, (G) trideoxyTTX and two analogs, (H) 4-epi-5,6,11-trideoxyTTX and another analog, and (I) 4,4a-anhydro-5,6,11-trideoxyTTX and 1-hydroy-4,4a-anhydro-8-epi-5,5,11-trideooxyTTX (see radicals of the analogs in the Table 1).
Marinedrugs 17 00028 g001
Table
Table 1. Tetrodotoxin (TTX) and analogs shown in Figure 1 and modified from European Food Safety Authority (EFSA) 2017 [45] and Yotsu-Yamasshita et al. (2007) [15,53].
Table 1. Tetrodotoxin (TTX) and analogs shown in Figure 1 and modified from European Food Safety Authority (EFSA) 2017 [45] and Yotsu-Yamasshita et al. (2007) [15,53].
ER1R2R3R4R5
TTX (*)HOHOHCH2OHOH
4-epiTTX (*)OHHOHCH2OHOH
6-epiTTX (*)HOHCH2OHOHOH
11-deoxyTTX (*)HOHOHCH3OH
6,11-dideoxyTTXHOHHCH3OH
8,11-dideoxyTTXHOHOHCH3H
11-oxoTTX (*)HOHOHCH(OH)2OH
11-norTTX-6,6-diolHOHOHOHOH
11-norTTX-6(R)-ol (*)HOHHOHOH
11-norTTX-6(S)-ol (*)HOHOHHOH
ChiriquitoxinHOHOHCH(OH)CH(NH3+)COO−OH
TTX-8-O-hemisuccinateHOHOHCH2OHOOC(CH2)2COO−
TTX-11-carboxylic acidHOHOHCOO−OH
TTX (*)HOHOHCH2OHOH
FR1R2R3R4R5R6
5-deoxyTTX(*)OHCH2OHHHOHH
5,11-dideoxyTTX (*)OHCH3HHOHH
5,6,11-trideoxyTTX (*)HCH3HHOHH
8-epi-5,6,11-trideoxyTTXHCH3HHHOH
GR1R2
4,9-anhydro-5,6,11-trideoxyTTXHOH
4.9-anhydro-8-epi-5,6,11-trideoxyTTXOHH
HR1R2R3R4R5
1-hydroxy-8-epi-5,6,11-trideoxyTTXOHHOHOHH
4-epi-5,6,11-trideoxyTTXHOHHHOH
IR1R2R3
4,4a-anhydro-5,6,11-trideoxyTTXHOHH
1-hydroxy-4,4a-anhydro-8-epi-5,5,11-trideooxyTTXOHHOH
Table
Table 2. Chemical abstract numbers (CAS) and relative toxicity of TTX analogs [58,59].
Table 2. Chemical abstract numbers (CAS) and relative toxicity of TTX analogs [58,59].
TTX AnalogsTEFCAS Number
TTX1.04368-28-9
11-oxoTTX0.75123665-88-3
11-deoxyTTX0.14-
11-norTTX-6(R)-ol0.17-
11-norTTX-6(S)-ol0.19-
4-epiTTX0.1698242-82-1
4,9-anhydroTTX0.0213072-89-4
6,11-dideoxyTTX0.02-
5-deoxyTTX0.01-
5,6,11-trideoxyTTX0.01-
4-CysTTX--
5,11-dideoxyTTX--
* TEF—toxic equivalency factor.
Table
Table 3. Characteristic symptoms of TTX human poisoning modified from Noguchi and Ebesu (2001) [66].
Table 3. Characteristic symptoms of TTX human poisoning modified from Noguchi and Ebesu (2001) [66].
LevelAffected SystemSpecific Symptoms
1NeuromuscularParesthesia of lips, tongue, and pharynx, taste disturbance, dizziness, headache, diaphoresis, pupillary constriction
GastrointestinalSalivation, hypersalivation, nausea, vomiting, hyperemesis, hematemesis, hypermotility, diarrhea, abdominal pain
2NeuromuscularAdvanced general paresthesia, paralysis of phalanges and extremities, pupillary dilatation, reflex changes
3NeuromuscularDysarthria, dysphagia, aphagia, lethargy, incoordination, ataxia, floating sensation, cranial nerve palsies, muscular fasciculation
Cardiovascular/pulmonaryHypotension or hypertension, vasomotor blockade, cardiac arrhythmias, atrioventricular node conduction abnormalities, cyanosis, pallor, dyspnea
DermatologicExfoliative dermatitis, petechiae, and blistering
4Respiratory failure, impaired mental faculties, extreme hypotension, seizures, loss of deep tendon and spinal reflexes
Table
Table 4. TTX detection methods, their limits of quantification (LOQs), limits of detection (LODs), and toxicity equivalency factors (TEFs) according to the European Food Safety Authority (EFSA). MBA—mouse bioassay; FLD—fluorescence detection; RB—receptor-based; LC—liquid chromatography; MS—mass spectrometry; HPLC—high-performance liquid chromatography; UVD—ultraviolet detection; SPR—surface plasmon resonance; TLC—thin-layer chromatography; GC—gas chromatography.
Table 4. TTX detection methods, their limits of quantification (LOQs), limits of detection (LODs), and toxicity equivalency factors (TEFs) according to the European Food Safety Authority (EFSA). MBA—mouse bioassay; FLD—fluorescence detection; RB—receptor-based; LC—liquid chromatography; MS—mass spectrometry; HPLC—high-performance liquid chromatography; UVD—ultraviolet detection; SPR—surface plasmon resonance; TLC—thin-layer chromatography; GC—gas chromatography.
Analysis MethodLODLOQ
MBA [12,36,52,89]1.1 μg·g−1 [89]-
Enzymatic assays [31,36,52,73,77,82,89,91,92,93]2 ng·mL−1 [92]-
TLC–MS [13,72]0.1 μg [72]-
HPLC–FLD [84,94,95]1.27 μg·g−1 [94]
GC–MS [76,84,95]0.5 μg·g−1 [76]1.0 μg·g−1 [76]
LC–MS/MS/UPLC–MS/MS [33,40,96,97,98]0.09–16 ng·mL−1 [33,40,96,97,98]5–63 ng·mL−1 [40]
SPR [30]0.3–20 ng·mL−1 [30]-
HPLC–FLD [15,32,99]40-100 ng·g−1 [15]-
Table
Table 5. The incidence of TTXs in the Indian Ocean. NPI—no poisoning incidents, MBA—mouse bioassay; FLD—fluorescence detection; LC—liquid chromatography; MS—mass spectrometry; HPLC—high-performance liquid chromatography; UVD—ultraviolet detection; TLC—thin-layer chromatography; GC—gas chromatography.
Table 5. The incidence of TTXs in the Indian Ocean. NPI—no poisoning incidents, MBA—mouse bioassay; FLD—fluorescence detection; LC—liquid chromatography; MS—mass spectrometry; HPLC—high-performance liquid chromatography; UVD—ultraviolet detection; TLC—thin-layer chromatography; GC—gas chromatography.
Producing SpeciesVectorSample TissueLocationCountryPoisoning DateTTXDetectionMaximum ConcentrationPoisoning VictimsReference
Australia
UnknownPuffer fish Lagocephalus scleratus Close to Fremantle HospitalAustralia13 May 1996TTXSymptomatology-3 people[23]
UnknownPuffer fish Lagocephalus scleratus Port HedlandAustralia1998TTXSymptomatology-1 person[24]
UnknownToad fish Tetractenos hamiltoni New South WalesAustralia1 January 2001 to 13 April 2002TTXSymptomatology-11 people[100]
UnknownToad fish Tetractenos hamiltoniUrine Australia2004TTXHPLC–UVD5 ng/mL7 people[80]
Serum20 ng/mL
Asian countries
UnknownPuffer fish KhulnaBangladeshApril 18 2002TTXSymptomatology-45 people[27]
UnknownPuffer fish Takifugu oblongusSkinKhulnaBangladesh18 May 2002TTXMBA18.9 MU/g36 people, 7 deaths[16]
Muscle4.4 MU
Liver4.9 MU/g
Gonads132.0 MU/g
Viscera categories 37.0 MU/g
Natore-
Dhaka
UnknownPuffer fishLiverKhulnaBangladesh24 July 2005TTXSymptomatology-6 people[22]
Unknown SkinKhulnaBangladesh25 March 2006TTXLC–MS/MS25.35 μg·g−1NPI[33]
Anhydro7.71 μg·g−1
11-Deoxy1.12 μg·g−1
Trideoxy15.31 μg·g−1
MuscleTTX1.64 μg·g−1
Anhydro-
11-Deoxy-
Trideoxy-
LiverTTX45.71 μg·g−1
Anhydro29.17 μg·g−1
11-Deoxy-
Trideoxy9.09 μg·g−1
OvaryTTX356.00 μg·g−1
Anhydro85.87 μg·g−1
11-Deoxy26.00 μg·g−1
Trideoxy 2,929.70 μg·g−1
UnknownPuffer fish DhakaBangladesh2008TTXSymptomatology-11 people[25]
UnknownPuffer Fish NarshingdiBangladeshApril and June 2008TTXSymptomatology-95 people, 14 deaths[26]
Natore
Dhaka
UnknownPuffer Fish Dhaka CityBangladeshOctober 2014TTXSymptomatology-11 people, 4 deaths[18]
UnknownPuffer fish-KhulnaBangladesh-TTXSymptomatology-37 people, 8 deaths[28]
UnknownPuffer fish Chelonodon patocaLiverBay of BengalIndiaJune 1998 to March 2001TTXMBA25.9 MU/gNPI[61]
Ovary183 MU/g
Sphaeroides oblongusLiver16 MU/g
Ovary7.9 MU/g
Lagocephalus inermisLiver5.5 MU/g
Ovary28.9 MU/g
Lagocephalus lunarisLiver5.9 MU/g
Ovary16.6 MU/g
UnknownPuffer fish Chelenodon potocaLiverBengal coastIndiaJune 2000–March 2001TTXMBA27.8 MU/gNPI[35]
Ovary156.7 MU/g
Takifugu oblongusLiver11.75 MU/g
Ovary29.1 MU/g
Lagocephalus lunarisLiver9 MU/g
Ovary30.1 MU/g
Lagocephalus inermisLiver5.7 MU/g
Ovary9.64 MU/g
Kytococcus sedentariusPuffer fish Arothron hispidusSkinAnnankil fish landings at ParangipettaiIndia2010TTXMBA-NPI[65]
Intestine-
Liver-
Cellulomonas fimiMuscle4.4 MU
Liver4.9 MU/g
Gonads132.0 MU/g
Bacillus lentimorbusViscera categories37.0 MU/g
Natore-
Dhaka-
UnknownPuffer fish Arothron stellatusMusclesParangipettaiIndia2016TTXHPLC–FLD, TLC–UVDQualitativeNPI[64]
Gonads4-epi
Liveranhydro
UnknownPuffer fish Takifugu oblongusSkinKasimedu fishing harbor, Chennai, Tamil NaduIndia2016TTXMBA75.88 MU/gNPI[62]
GC–MS16.5 MU/g
HPLC18 MU/g
LiverMBA143.33 MU/g
GC–MS32.5 MU/g
HPLC48 MU/g
OvaryMBA163 MU/g
GC–MS34.5 μg
HPLC51 μg
UnknownPuffer fish-JohorMalaysiaMay 2008TTXSymptomatology-34 people[68]
UnknownCarcinoscorpius rotundicaudaUrineKota MaruduMalaysiaJune–August 2011TTXGC–MS1.3–602 ng/mL30 people[88]
UnknownPuffer fish Xenopterus naritusMuscleManggutMalaysiaFebruary and July 2013TTXLC–MS/MS27.19 μg/gNPI[63]
Kaong16.09 μg/g
UnknownPuffer fish Lageocephalus scitalleratus Alexandra HospitalSingapore2013TTXSymptomatology 1 person[20]
UnknownTetraodon nigroviridisReproduc tive tissueSatunThailandApril to July 2010TTXLC–MS/MS, MBA63.57 MU/gNPI[36]
Liver97.08 MU/g
Digestive tissue43.33 MU/g
Muscle22.12 MU/g
Arothron reticularisReproductive tissue-
Liver2.08 MU/g
Digestive tissue3.16 MU/g
Muscle4.02 MU/g
African countries
UnknownPuffer fish Lagocephalus lunarisGonadsNational Research Center, Dokki, Cairo,EgyptSeptember 1990 through May 1991TTXTLC–UVD, MBA752 MU/gNPI[34]
Liver246 MU/g
Muscles127 MU/g
Digestive tract221 MU/g
Skin119 MU/g
UnknownPuffer fish Lagocephalus sceleratusGonadsAttaka fishing harborEgyptOctober 2002 and June 2003TTXMBA3950 MU/gNPI[37]
UnknownPuffer fish Lagocephulus scleratusMuscleSuez GulfEgypt23 December 2004TTX 7 people[21]
UnknownPuffer fish Nosy Be IslandMadagascarJuly 1998TTXMBA16 UM/g3 people, 1 death[19]
UnknownPuffer fish Lagocephalus sceleratusLiverReunion IslandReunion Island10 September 2013TTXMBA, LC–MS/MS95 MU/g10 people[29]
Flesh5 MU/g
UnknownPuffer fish, Tetraodontidae family ZanzibarTanzania TTXSymptomatology-1 death[17]

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MDPI and ACS Style

Tamele, I.J.; Silva, M.; Vasconcelos, V. The Incidence of Tetrodotoxin and Its Analogs in the Indian Ocean and the Red Sea. Mar. Drugs 2019, 17, 28. https://doi.org/10.3390/md17010028

AMA Style

Tamele IJ, Silva M, Vasconcelos V. The Incidence of Tetrodotoxin and Its Analogs in the Indian Ocean and the Red Sea. Marine Drugs. 2019; 17(1):28. https://doi.org/10.3390/md17010028

Chicago/Turabian Style

Tamele, Isidro José, Marisa Silva, and Vitor Vasconcelos. 2019. "The Incidence of Tetrodotoxin and Its Analogs in the Indian Ocean and the Red Sea" Marine Drugs 17, no. 1: 28. https://doi.org/10.3390/md17010028

APA Style

Tamele, I. J., Silva, M., & Vasconcelos, V. (2019). The Incidence of Tetrodotoxin and Its Analogs in the Indian Ocean and the Red Sea. Marine Drugs, 17(1), 28. https://doi.org/10.3390/md17010028

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