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Toxin in seafood causes kidney damage in mice at levels considered safe for consumption

By Dawn Brazell | News Center | February 7, 2014


Seafood

FDA may need to reconsider what levels of domoic acid in shellfish and fish are safe.

Photo Illustration

It may not seem that Navy-trained sea lions, a plate of seafood, and a kidney research lab at the Medical University of South Carolina would have much in common.

It turns out they do.

Dr. P. Darwin Bell

Researchers at MUSC have found that domoic acid, which accumulates in seafood and is toxic to the brain, also damages kidneys at concentrations 100 times lower than what causes brain damage. These findings, out today in a study appearing in the Journal of the American Society of Nephrology, points to the need for more research, especially since the Federal Drug Administration (FDA) has set a legal limit of domoic acid in seafood based primarily on its adverse effects on the brain.

 P. Darwin Bell, Ph.D., MUSC Division of Nephrology Research Endowed Chair, Jason Funk, Ph.D., MUSC division of Nephrology, and their colleagues said the study uncovers new ground and raises important questions.

“We want to generate awareness about this and the fact that this is something that may need to be looked at further, especially by the FDA in controlling exposure,” Funk said.

Ninety-nine percent of the existing research focuses on the neurologic effects of domoic acid. There is little evidence of its effect on other organs, said Bell. “The fact that we’ve found that domoic acid is so highly toxic to the kidney is novel and new and has not been recognized at all. There’s a view that repeated injury to the kidney accumulates over time and can lead to kidney failure. What we worry about is the fact that you’re getting these small exposures to domoic acid and have this cycle of injury, recovery – injury, recovery that can lead to renal failure at some point down the road.”

Some believe this type of exposure may be much more toxic to the elderly, young children, people with pre-existing kidney disease, and perhaps pregnant women, but there will have to be many more studies before those guidelines can be set. It’s too early “to set off alarm bells” until more studies can be done to validate results, said Bell.

Neutrophil gelatinase-associated lipocalin (NGAL), a sensitive and early marker of kidney injury, was detected by immunohistochemistry in the renal cortex of mice exposed to domoic acid, which was absent in mice administered an injection of saline vehicle (NGAL = brown stain, Hematoxylin counterstain).

It does bear monitoring, though.

“There’s warming of the ocean and an increase of the amount of algae in the ocean – this toxin is produced by algae. So there are these algae blooms that produce domoic acid. It doesn’t get broken down so it just stays at the bottom of the oceans and gets taken up by mussels, scallops and fish. A recent report stated that over 50 percent of bottle-nosed dolphins in Sarasota Bay in Florida now have detectable levels of domoic acid.”

Bell said that only in the last few years have domoic acid and other toxins been detected in the Gulf. “The increase in domoic acid levels in our oceans is becoming more and more alarming.”

Previously, it was more of a West coast problem, which brings up how sea lions factor into the story. Bell said a catalyst for the research came from the work of MUSC colleague Michael Gregory Janech, Ph.D., who studies sea lions enlisted in the U.S. Navy Marine Mammal Program to patrol the harbor and provide protection for ships.

“They eat anchovies and sardines that have domoic acid. They get this electro-excitatory neurotoxicity, and they go crazy and they die. The Navy spends a huge amount of money to train these sea lions so he’s been looking at how to predict if a sea lion is getting domoic acid poisoning. One of the things they have found is the functioning of the kidney seems to be altered and that led us to do this study on mice.”

Dr. Jason Funk

Though the brain is protected somewhat by the blood-brain barrier, the kidney is the primary mode of excretion. Funk said one of the first steps in their study was to expose mice to the acid to see where it distributed in the body. “It was like four to five times higher in the kidney compared to any other organ we tested including brain. That finding validated us going farther in this study.”

Funk said the next step is to study chronic repeated exposures to see what impact it would have on kidney function and to determine if these findings translate to human populations. “Our work is the first initial step showing that the kidney accumulates this toxin and that it causes kidney damage. It’s certainly something that the FDA and other governing agencies, as well as researchers, need to be aware of – that the kidneys are susceptible to injury at extremely low levels of this toxin.”


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Resources >>

MUSC Division of Nephrology

Dr. Phillip D. Bell research

MUSC Marine Biomedicine

Journal of the American Society of Nephrology

 
 
 

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