More about the toxin, Domoic acid..

Domoic acid is a potent neurotoxin produced by a naturally occuring Harmful Algal Bloom. Specifically, it is made by a microscopic, red-brown, salt-water plant, or diatom calledNitzchia pungens. The toxin produced by these diatoms is concentrated in shellfish such as mussels and causes Amnesic Shellfish Poisoning when the contaminated shellfish are eaten. What makes this toxin more dangerous is the fact that it is not destroyed after cooking, which can cause many unsuspecting consumers to fall ill with Amnesic Shellfish Poisoning..

How dangerous is Domoic Acid?
Domoic acid is a toxin that affects the brain, specifically the  hippocampus, and affects both animals and humans. It may cause severe health implications.

Fig 1- Left: normal California sea lion brain section. Right: a not so normal one that has been affected by domoic acid exposure; notice the shrunken hippocampus in the center of the brain section

In humans..
Domoic Acid causes Amnesic Shellfish Poisoning(ASP).  ASP can be a life-threatening syndrome, and is characterized by both gastrointestinal and neurological disorders.
After consumption of the contaminated shellfish, Gastroenteritis usually develops.

Symptoms include:
-Nausea
-Vomiting
-Abdominal cramps
-Diarrhea.

In severe cases, neurological symptoms also appear, usually within 48 hours of toxic shellfish consumption.

Symptoms include:
-Dizziness
-Headache
-Seizures
-Disorientation
-Short-term memory loss
-Respiratory difficulty
-Coma


How does Domoic Acid work?

To understand this, we first have to introduce a new molecule- Glutamic acid.

Fig 2: Glutamic Acid structure

So what’s so important about this molecule?
Glutamate (the ionized form of glutamic acid) is a neurotransmitter, a molecule used to send a message from one nerve cell to another, and plays an important role in thought, learning, and memory. Binding of glutamate to a glutamate receptor causes the opening of channels allowing embedded on the membrane of the receiving nerve cell, the receptor opens channels in the membrane that allow calcium ions to flow into the cell. The influx of charge causes a voltage to build up across the cell membrane, and the nerve cell fires, passing the signal on to the next nerve cell.

However, too much glutamate acts as an excitotoxin- which kills cells by exciting them too much. This will eventually lead to an excitotoxic cascade, which plays an important role in brain injury and neurodegenerative diseases.

Now, back to Domoic Acid and how it causes damage to the brain.

Domoic acid’s structure is similar to glutamic acid.As a result, nerve cells mistakenly recognize domoic acid as glutamic acid- a fatal error.  Its five-sided ring makes it less flexible than glutamate, which causes it to bind very tightly to glutamate receptors. As a result, the excitatory effect of domoate is 30 to 100 times more powerful than that of glutamate, resulting in an excitotoxic cascade.

What is being done now to prevent another outbreak of Amnesic Shellfish Poisoning?
Luckily for us, commercial shellfish and seafood are now monitored regularly for domoic acid, using HPLC(High-Performance Liquid Chromatography) to identify the toxin. The screening and testing procedures have so far been successful- not a single instance of domoic acid poisoning in humans has been reported since the 1987 outbreak.

Read on to our next post to find out how we can carry out Quantitative Analysis on Domoic Acid!

Citations

1. Egglilng, S. (n.d.). Common names of amino acids. Retrieved from http://dl.clackamas.cc.or.us/ch106-05/common.htm

2. Foley, S. (2009, July 01). Domoic acid-toxipedia. Retrieved from http://toxipedia.org/display/toxipedia/Domoic Acid

3. Senese, F. (2010, February 15). General chemistry online: The poisoned needle. Retrieved from http://antoine.frostburg.edu/chem/senese/101/features/domoic.shtml

4. Human illness associated with hab. (n.d.). Retrieved from http://www.whoi.edu/science/B/redtide/illness/illness.html

5. Potera, C. (2009). Harmful algal blooms: An unexpected deep-sea diver. Environ Health Perspect, 117(6), Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702427/

 6. The marine mammal centre: Domoic acid toxicity. (n.d.). Retrieved from http://www.marinemammalcenter.org/science/top-research-projects/domoic-acid-toxicity.html

Importance of Analytical Chemistry-What do you do when you’re dealing with an unknown, dangerous toxin?

Toxin strikes in Canada

In 1987, a mysterious syndrome struck in Canada. Over a hundred people became extremely ill within hours after dining on cultured blue mussels in restaurants around Prince Edward Island in Canada.

It quickly became apparent that this was no ordinary outbreak of food poisoning. Vomiting, cramps, diarrhea, and incapacitating headaches were followed by confusion, loss of memory, disorientation, and (in severe cases) seizures and coma. A few exhibited emotional volatility, with uncontrolled crying or aggressiveness. Three elderly victims died.

A tragic symptom of poisoning was the destruction of short term memory in about one quarter of the survivors. The most severely affected lost memories several years old. For twelve of the victims, the loss of short term memory was permanent.

This mysterious syndrome was called Amnesic Shellfish Poisoning. This sort of neurological damage due to food poisoning had never been encountered before. To prevent further injury and loss of life it was imperative that the toxic agent be isolated and identified as quickly as possible. A team of marine biologists and chemists was assembled by Canada’s Department of Fisheries and Oceans (DFO) to work on the problem.

Carrying out Qualitative Analysis on the unknown toxin

As the mussel samples were extremely complex, isolating the toxin was no easy task. Scientists first needed to separate the numerous compounds so the toxin could eventually be isolated. They did this through step by step physical separation methods, where mice were exposed to each fraction of the separation. Fractions found to be toxic were then retained for further analysis. Take a look at this diagram to see what methods they used! 

    

Fig 1: Identifying the toxin

Eventually, after a final separation of the sample by HPLC and a confirmation by high voltage paper electrophoresis, the isolated toxin underwent Mass Spectrometry for identification.

The toxin was found to be… Domoic Acid!

 

Fig. 2- Domoic Acid

So THIS compound was responsible for the mysterious food poisoning incident.

Learn more about this dangerous substance in our next post. Stay tuned!

Citations

1. Senese, F. (2010, February 15). General chemistry online: The poisoned needle. Retrieved from http://antoine.frostburg.edu/chem/senese/101/features/domoic.shtml

2. Habs and biotoxins: Marine biotoxins- domoic acid poisoning. (n.d.). Retrieved from http://www.nwfsc.noaa.gov/hab/habs_toxins/marine_biotoxins/da/index.html