Domoic Acid Toxicity

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Transcript Domoic Acid Toxicity

Presented by Natalie Nieto and Judea Wiggins
Amnesic Shellfish Poisoning– What interested us?
Throughout the course of Biology of Toxins, we
have learned that there is “no free lunch.”
Many substances we view as harmless can
often pose a serious threat. As amnesic
shellfish poisoning results from the consumption
of seafood containing dangerous levels of
domoic acid, we felt this to be an interesting
topic to pursue. Seafood is consumed widely
across the globe, therefore becoming more
aware of its toxic possibilities is essential.
Amnesic Shellfish Poisoning – How Will We Present It?
In this presentation, we will discuss amnesic shellfish poisoning (ASP) in all its entirety,
General overview of what constitutes a substance as ‘toxic’
Introduction and background information of amnesic shellfish poisoning
A detailed overview of domoic acid
The role the environment plays in ASP, specifically algal blooms
Toxic effects and symptoms
Treatment options
Most recent outbreak
Research findings
Suggestions for further study
Toxin – What is it?
A toxin is a substance produced by an organism that has an adverse
effect on another organism.
The “no free lunch” principle indicates every substance to hold the
potential of being toxic under the right conditions, specifically the dose
of the substance and the organism exposed to the substance.
A toxic substance may function as a defensive mechanism, an offensive
mechanism, or both.
For marine toxics, a naturally-occurring chemical is produced by a marine
organism that becomes toxic to humans upon consumption of
contaminated seafood.
Amnesic Shellfish Poisoning – What is it?
Amnesic shellfish poisoning (ASP) is an illness caused by the ingestion
of contaminated shellfish, i.e. mussels, clams, oysters, and even
Dungeness crabs that prey on shellfish.
Shellfish become ‘contaminated’ when they consume phyloplankton, or
algae, containing high concentrations of the marine toxin, domoic acid.
Domoic Acid – When was it discovered?
The first diagnosed case of Amnesic
Shellfish Poisoning occurred in 1987
after 3 deaths and 100+ acute
intoxications took place in Canada,
following consumption of blue
However, it wasn’t until 1998 that
domoic acid toxicosis was first
diagnosed in marine mammals by
the Marine Mammals Center.
Domoic Acid – What is it?
Domoic acid is an excitatory
neurotransmitter and derivative of
glutamine; it is also a conditionally
essential amino acid –not synthesized by
the body, but instead dietary-obtained.
Domoic acid is produced by diatoms of the
genus, Pseudo-nitzschia.
Diatoms are the most common type of
phytoplankton: single-celled,
photosynthetic algae.
These diatoms can be found in coastal
waters all around the world, and serve as
a major nutrient source for many plankton
consumers, such as whales, shrimp, fish, and
Pseudo nitzschia – Why do they produce domoic acid?
Research has shown that the presence of iron, or lack there of, plays a
role in governing phytoplankton growth; lower amounts of available
iron are associated with lower growth rates.
More than 99% of dissolved iron in the ocean is bound to other
complex elements such as saccharides; phytoplankton have devised
methods to access this bound iron.
Scientist speculate that this particular genus produces domoic acid as a
function of the iron uptake mechanism by increasing affinity.
This, in turn, gives P. nitzschia a competitive edge against other
phytoplankton for proliferation in times where iron is less abundant.
Domoic Acid – What is its mechanism?
Domoic acid acts as a glutamate
agonist, upregulating glutamate
When glutamate is expelled from the
pre-synaptic cell’s vesicle, it then
binds to the glutamate receptor,
NMDA, which triggers calcium
channels to open.
Domoic Acid – What is its mechanism?
With glutamate receptors
being overwhelmed by
glutamate ligands, calcium
channels do not close on the
postsynaptic cell.
Influx of calcium on the
postsynaptic cell leads to
constant excitatory action
potentials being produced.
Calcium Overload – Why is it dangerous?
Excessive stimulation of neurons by
excitatory action potentials leads to
excitotoxicity; under these conditions, cells
are either damaged or undergo apoptosis.
Constant calcium influx into cells
inadvertently activates degradative
enzymes such as phospholipases,
endonucleases, and proteases that destroy
the lipid bilayer, DNA, and other
components of the extracellular matrix in
the central nervous system.
Domoic Acid – What is its pathology?
In acute exposure, brain damage occurs in the form of neurodegenerative
changes such as neuronal shrinkage, edema, cytoplasmic swelling, and
numerous other neurological symptoms.
The hippocampus, memory center, is a specific target site for domoic acid;
this is why loss of short term memory is a notable symptom.
The inner nuclear layer of the retina of the eye may also undergo damage,
along with spinal chord lesions, leading to motor sensory abnormalities due
to damage of the gray matter.
Direct cardiotoxicity is also observed, but is unlinked to the effects of
domoic acid on cardiovascular control centers in the central nervous system.
Algal Blooms – What role do they play?
While diatoms are a normal component of all aquatic environments, when
they reproduce in significant numbers, they result in algal blooms.
This overproduction of algae leads to an abundance of dead organic
matter, and thus a subsequent increase in the production of bacteria.
Bacteria consume dissolved oxygen in the water, making it difficult for
aquatic life to survive.
Algal blooms become harmful by the overabundant production of
phosphorus and nitrogen within the surrounding water source, leading to the
hyper-production of domoic acid-containing algae.
As aquatic animals like shellfish feed upon this toxic algae, our seafood
sources become contaminated.
Algal Blooms – What is different between fish and humans?
Many aquatic organisms, especially
shellfish, filter feed on this toxic algae.
In overconsumption, domoic acid
builds up in their tissues, but causes no
apparent physiological harm.
Problems occur, however, when humans
unknowingly consume contaminated
shellfish, thus leading to the onset of
amnesic shellfish poisoning.
Algal Blooms – How can we identify them?
Algal blooms may occur in both freshwater and
marine environments.
The photosynthetic pigment of the infected
algal cells determines the color affected water
sources depict.
For instance, cyanobacteria algal blooms are
known as blue-green algae based on the bluegreen tint observed in affected water areas.
With phytoplankton, a red or brown tint is
observed, which is why the affected water
area is often referred to as a “red tide.”
Amnesic Shellfish Poisoning – What are the symptoms?
Within 24 hours of consumption of
contaminated seafood, an onset
of the following symptoms results:
 Diarrhea
 Nausea
 Abdominal cramps
Within 48 hours, more severe
poisoning cases will result in
serious neurological symptoms of:
 Dizziness
 Confusion and disorientation
 Permanent loss of short-term
 Motor weakness
 Cardiac arrhythmias
 Coma
 Death
Allergy to Shellfish – Is ASP the same thing?
When someone is allergic to shellfish, their body produces an immune
response to the consumption of shellfish.
While this immune response can range from mild to severe, it is not
brought on by actual toxicity.
Instead, the body is responding to the shellfish protein of allergen by
triggering the production of antibodies and the release of histamine.
Amnesic Shellfish Poisoning – How is it treated?
Unfortunately, no highly effective antidote exists to combat the
effects of domoic acid toxicity that result in amnesic shellfish
Positive effects have been observed, however, in reducing seizures
with diazepam, a muscle relaxer, administered in conjunction with
phenobarbital, an epilepsy deterrent, intravenously.
In the event of respiratory failure, the best means of treatment is to
administer life support until the toxin has been expelled from the
victim’s body.
Safe Seafood Consumption – How can I prevent ASP?
The best means of protection is practicing prevention.
It is important to note that domoic acid is not neutralized by cooking
the contaminated shellfish.
Commercial and local shellfish harvesting companies are strictly
monitored by federal and state health departments.
Levels of domoic acid are routinely tested to ensure safe seafood
In the event that levels of domoic acid are detected over 20
micrograms per gram of wet weight, harvesting must be halted in that
area until levels decrease over time.
Safe Seafood Consumption – How can I prevent ASP?
According to the CDC, there are a few
general guidelines one should adhere to
when consuming seafood:
 Consuming
raw seafood or shellfish holds
great potential to cause illness due to the
various bacteria found in seawater and
should be avoided by persons with
weakened immune systems
 Seafood should be kept on ice or
refrigerated at temperatures below 38°F
Safe Seafood Consumption – How can I prevent ASP?
The CDC also recommends more specific guidelines to safe
consumption of seafood:
 Refrigeration
of fresh tuna, mackerel, grouper, and mahi mahi is essential to
prevent poisoning
 Barracuda, especially those obtained from the Caribbean, should always be
 Remaining up-to-date with local and national health official advisories
regarding algal blooms, bacterial growth, and “red tide” conditions is
 Avoid finfish or shellfish that are used as bait as they are not held under the
same safety food regulations
Regulation – What is the Government doing?
The U.S. Food and Drug Administration is
responsible for regulating seafood guidelines.
The Federal Food, Drug and Cosmetic Act, the
Public Health Act, and similar regulations aim to
prevent the occurrence of marine toxic poisoning
through the publication of the Fish and Fisheries
Products Hazards and Controls Guidance manual.
This serves to provide up-to-date science and
policies regarding potential hazards of seafood.
Regulation – What is the Government doing?
The guidelines presented by the FDA serve as reference to fish and
fishery product regulatory programs globally with regulations
 Procedures
for the safe and sanitary processing and importing of fish and
fishery products
 Specific
 Enhanced
guidelines for the processing and importing of crabmeat
aquaculture and seafood inspection
Guidance – What is the Government doing?
In addition to providing strict regulations, the FDA provides extensive
guidance by which fish industries may follow to prevent seafood
poisoning, including:
 Guidance
for purchasing reef fish species
 Guidance for interstate commerce
 Processes for inspection and certification of seafood export
 Guidance for implementing a HACCP (Hazard Analysis and Critical Control
Points) prevention system
Statistics – How often does this occur?
According to the CDC, approximately 30 cases of marine toxin
poisoning occur in the United States yearly.
Unfortunately, there are no requirements to reporting cases of marine
toxin poisoning.
Some cases are mild and therefore go undiagnosed.
As a result, it is likely the number of poisonings is much greater than
we estimate, and in turn, makes it difficult to specifically estimate ASP
Statistics – How often does it occur?
Based on the data available,
however, it is estimated that
one person dies every 4 years
from marine toxin poisoning.
Interestingly enough, poisoning
is more common during the
summer months due to better
growing conditions of
phytoplankton and
development of algal blooms.
Domoic Acid Toxicity in the News – When was the last outbreak?
In 2014, a population of shellfish, specifically mussels, were identified
to contain dangerous levels of domoic acid.
As a result, the California Department of Public Health advised
consumers to avoid recreationally harvested shellfish from Monterey
and/or Santa Cruz.
As certified, commercial harvesters and dealers of shellfish are under
strict regulations and mandated to frequent screening for toxins,
shellfish obtained from these sources were approved during the
Research – What did they find?
In a recent study, researchers focused on a
“new” area that domoic acid from amnesic
shellfish poisoning may affect, the kidneys.
As the kidneys are responsible for expelling
the toxin via renal filtration, they also
express ionotropic glutamate receptors.
With increased production of glutamate by
its agonist, domoic acid, researchers
conducted an experiment on mice to
determine the renal effects of domoic acid.
Research – What did they find?
Upon administering neurotoxic dose(s)
to experimental mice, researchers
discovered an accumulation of
domoic acid in the kidneys,
comparable to renal vascular and
tubal damage associated with acute
tubular necrosis, apoptosis, and renal
tubular cell desquamation.
These effects result in toxic
vacuolization and mitochondrial
swelling, characterizing cellular
Fig.1. Cellular damage, including endothelial cell
and mitochondrial swelling and vacuolization.
Summary – What have we learned?
We have presented a detailed explanation of amnesic shellfish
poisoning, including its definition, symptoms, treatment, and prevention.
Addressing the key component making shellfish toxic, we have
provided detailed and pertinent information regarding domoic acid,
most specifically the mechanism by which the human body is harmed.
With this presentation, we have provided adequate and valuable
information to consider when consuming shellfish.
Conclusion – Where do we go from here?
Based on the research findings of the effects on the kidneys,
regulatory policies could be modified to account for the additional
harm caused, specifically in determining “safe” doses of domoic acid.
With little information known regarding domoic acid’s effect on
shellfish, it would be interesting to explore why domoic acid does not
produce the same harmful effects it does on humans.
Lastly, as the “no free lunch” principle also applies, it would be
intriguing to speculate why only this specific algae species produces
the toxin, i.e. what is the cost and benefit of doing so.
Funk, J.A., Janech, M.G., Dillon, J.C., Bissler, J.J., Siroky, B.J., and Bell, P.D. (2014). Characterization of renal toxicity in mice
administered marine biotoxin domoic acid. Journal of the American Society of Nephrology, 25.
Prince, E.K., Irmer, F., and Pohnert, G. (2013). Domoic acid improves the competitive ability of Pseudo-nitzschia delicatissima
against the diatom Skeletonema marinoi, 11(7).