New insights into the causes of human illness due to consumption of azaspiracid contaminated shellfish.
Azaspiracid (AZA) poisoning was unknown until 1995 when shellfish harvested in Ireland caused illness manifesting by vomiting and diarrhoea. Further in vivo/vitro studies showed neurotoxicity linked with AZA exposure. However, the biological target of the toxin which will help explain such potent neurological activity is still unknown. A region of Irish coastline was selected and shellfish were sampled and tested for AZA using mass spectrometry. An outbreak was identified in 2010 and samples collected before and after the contamination episode were compared for their metabolite profile using high resolution mass spectrometry. Twenty eight ions were identified at higher concentration in the contaminated samples. Stringent bioinformatic analysis revealed putative identifications for seven compounds including, glutarylcarnitine, a glutaric acid metabolite. Glutaric acid, the parent compound linked with human neurological manifestations was subjected to toxicological investigations but was found to have no specific effect on the sodium channel (as was the case with AZA). However in combination, glutaric acid (1 mM) and azaspiracid (50 nM) inhibited the activity of the sodium channel by over 50%. Glutaric acid was subsequently detected in all shellfish employed in the study. For the first time a viable mechanism for how AZA manifests itself as a toxin is presented.
Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, BT9 5AG, UK.
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OP
Chevallier
Beaumont Research Institute, 3811 W Thirteen Mile Road, Royal Oak, MI, 48073.
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SF
Graham
Department of Pharmacology, Faculty of Veterinary, Campus Lugo, USC, 27002 Lugo, Spain.
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E
Alonso
Marine Institute, Rinville, Oranmore, Co. Galway, Ireland.
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C
Duffy
Marine Institute, Rinville, Oranmore, Co. Galway, Ireland.
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J
Silke
Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, BT9 5AG, UK.
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K
Campbell
Department of Pharmacology, Faculty of Veterinary, Campus Lugo, USC, 27002 Lugo, Spain.
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LM
Botana
Advanced Asset Technology Centre, Institute for Global Food Security, Queen's University Belfast, Stranmillis Road, Belfast, BT9 5AG, UK.
C T
CT
Elliott
D000818:Animals; D049872:Bivalvia / Q000033:anatomy & histology / Q000737:chemistry; D002331:Carnitine / Q000031:analogs & derivatives / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D004196:Disease Outbreaks; D005517:Foodborne Diseases / Q000209:etiology*; D005977:Glutarates / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D008387:Marine Toxins / Q000737:chemistry* / Q000633:toxicity*; D012758:Shellfish / Q000032:analysis* / Q000633:toxicity*; D015222:Sodium Channels / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry* / Q000633:toxicity*; D000095702:Polyether Toxins
D002331:Carnitine; D005977:Glutarates; D008387:Marine Toxins; D015222:Sodium Channels; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins; C053168:glutarylcarnitine; C035736:glutaric acid