Could Tough Toadfish Be Key to Medical Mystery?

Based on a segment by Steve Greenberg
National Geographic Today
January 27, 2003
Handsome, they're not. But toadfish could hold the answer to a
medical mystery.

What makes the toadfish unique is that it can survive in ammonia concentrations that would kill almost every other creature, including man. That fact is important because high ammonia concentrations are associated with many diseases including liver problems.

"The remarkable thing about these fish is that they can tolerate between 10 and 20 times more ammonia than our bodies—they are the champions of ammonia tolerance," said Patrick Walsh, a marine biologist at the University of Miami in Coral Gables, Florida, who has been studying toadfish for years.

"If we can figure out the mechanisms toadfish are using, then we can develop a clinical strategy or drug, to make humans tolerate more ammonia during disease onsets," said Walsh.

When the liver is damaged, whether by environment, genetics, or alcoholism, it is unable to filter and excrete ammonia—a waste product. The tissue most sensitive to ammonia is the brain.

Liver Fails, the Brain Fails

That's why doctors say, "when the liver fails, the brain fails." By understanding how the toadfish tolerates ammonia, scientists hope to halt its toxic effects in humans.

"When our brains encounter ammonia they convert it to the amino acid glutamine. It's believed the glutamine buildup in the brain causes cells to swell, and as the brain swells it causes pressure to build up which cuts off circulation to vital parts of the brain," said Walsh.

In the human brain glutamine is sort of a dead-end product, but the toadfish might be able to rid the brain of glutamine and metabolize it in other organs such as in muscles, kidneys, and liver, said Walsh. "What we might be able to do is to mimic what the toadfish is doing with a drug that enhances our brain's ability to rid itself of glutamine," he added.

Examining a slice of brain under the microscope, Miguel Perez, a professor of neurology and neuroscience at the UM School of Medicine, compares brains from rats and toadfish, searching for clues as to how the toadfish protects itself from ammonia.

Perez says this toadfish research could have profound medical implications. "Understanding the mechanisms of how the toadfish survives these toxins will help us develop therapies for stroke, liver disease, heart attack and brain injury," said Perez.

They're called toadfish because they sound similar to a toad. Toadfish are the fourth most common fish found in Miami's Biscayne Bay, but though they are plentiful in the bay, they are not easily seen.

Toadfish tend to reside in still, shallow water and bury themselves in the sandy bottom. Even in a laboratory tank, they make their home in any closed, confined space. "They have a really strong jaw, with stubby teeth that are meant to crush mollusk shells, crustaceans and things like that," said Walsh.

"It is ironic. You look at this fish that has a face only a mother toadfish could love, it sits on the bottom, and hides from predators. But to think that this lowly, ugly fish could help us with human health is pretty remarkable. It never ceases to amaze me that out there in nature there are all of these secrets waiting to be unfolded," said Walsh.

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