MUSC researchers have established that a toxin commonly found in some seafood damages kidneys at concentrations much lower than those approved as safe for the brain. Domoic acid (DA), which is produced by ocean algae, has been known for decades to be toxic to the brain. The U.S. Food and Drug Administration (FDA) bases the legal limit of DA in seafood on its neurotoxicity. But in an MUSC study in mice, investigators found that DA damages kidneys at a concentration 100 times lower than that which causes brain damage. The findings are published in the June 2014 issue of theJournal of the American Society of Nephrology.
P. Darwin Bell, PhD, Professor in the Division of Nephrology, and Jason Funk, PhD, a postdoctoral research fellow, were co-authors of the article. Other investigators’ earlier research in sea lions had shown that DA altered kidney function, but little follow-up research had been done. Dr. Bell and Dr. Funk wanted to advance understanding of this agent of renal injury. The laboratory team injected lower and lower doses of the toxin into mice and eventually found the toxicity threshold to be very low and the damage immediate. “In our lab, we saw that domoic acid caused a striking degree of renal damage within minutes to hours,” Dr. Bell reports. “The FDA sets the limit of domoic acid that can be consumed by humans at 20 parts per million. The government says below this it doesn’t cause any neurologic effects, but the kidneys are affected at levels one hundred times lower than this concentration.”
The primary reason why DA may be more toxic to the kidneys than the brain is that the brain is protected by the blood-brain barrier. The kidneys, more than any other organ system, accumulate DA before elimination because systemic DA is predominantly excreted via renal glomerular filtration.
The Bell laboratory team examined biomarkers, including the kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), and found elevated levels of these markers in the kidneys and urine of exposed mice. They then examined changes in the expression of acute-phase genes that have been associated with DA poisoning. “Even at the lowest levels that we tested, which were well below the accepted neurotoxic doses,” Dr. Funk says, “we saw a transient change in gene expression, which suggested that the kidneys were particularly susceptible to DA toxicity.”
DA accumulates in mussels, clams, scallops, anchovies, and sardines, but it is now appearing in larger sea creatures such as fish and dolphins as DA becomes more prevalent in coastal regions. DA is heat-resistant and cannot be cooked out of food. Drs. Bell and Funk plan to continue to look at the molecular mechanisms by which this toxin does its damage and hope to partner with clinical researchers to study the effects of DA in humans.