Lightning strikes twice for iodine as potentially life-saving intervention

From the Roth Lab, Basic Sciences Division

Iodine has long held a hallowed position in the pantheon of public health. It is a key ingredient in the production of thyroid hormone, an important regulator of growth and intellectual development. But in a cruel twist of fate, it is also dangerously deficient in the natural diets of billions of people around the world, putting them at risk of physical and intellectual disabilities. Thus, beginning in the early 20th century, large-scale nutritional supplementation of iodine, in the form of iodized salt, provided a cheap and effective method to rescue untold millions from the scourge of iodine deficiency. It seems, though, that this humble element has more tricks up its sleeve. In a new article published in the journal Critical Care Explorations, Dr. Mark Roth from the Basic Sciences Division at Fred Hutch and colleagues identify Iodine as a central component of an evolutionarily conserved strategy to protect tissues in the face of severe stress.

The tissues in our body spend most of their time in a homeostatic state of relative calm. This equilibrium is, however, occasionally punctuated by dangerous moments of extreme stress during which it is crucial, in both the body’s own responses and in medical interventions, to minimize tissue damage while working to recover to a safe state. One such condition is ischemic stress: during a heart attack, stroke, or traumatic injury, loss of blood supply can starve a tissue of oxygen and place it at high risk of death. Somewhat counter-intuitively, Roth’s group points out, “we have learned that much of the loss of cell and tissue viability is caused not by low oxygen itself but rather by its return and the increase in reactive oxygen containing molecules such as hydrogen peroxide which can lead to cell and tissue damage.” It is in this context that iodine once more may provide a solution. In addition to its function in thyroid hormone production, the Roth lab has found that iodine belongs to a class of “elemental reducing agents” that can catalytically break down hydrogen peroxide and, in this capacity, perhaps serve as a valuable tool to protect hypoxic tissues from damage during reoxygenation.

Roth’s team, including Akiko Iwata, Mery Wick and Mike Morrison, reasoned that if iodine possesses a protective ability, organisms may have naturally evolved strategies to deploy it to tissues facing hypoxic stress. “Some animals, such as the arctic ground squirrel, have evolved innate resistance to hypoxia”, they explain. “what enables some people and animals to better survive the stress of low oxygen?” To address this question, the team collaborated with Seattle-area hospitals and with the lab of Dr. Kelly Drew, of the Institute of Arctic Biology at the University of Alaska Fairbanks, to examine the physiological response to hypoxic conditions in human trauma patients and in hibernating arctic ground squirrels. By monitoring iodine levels in the blood, they found that trauma and hibernation both caused a release of large amounts iodine into the blood, including an astounding 17-fold increase in trauma patients. To determine whether these increases in blood iodine may actively protect hypoxic tissues, the Roth group designed a laboratory experiment in which they temporarily blocked blood flow to the leg muscles of mice. Next, they injected exogenous iodine into the blood prior to reperfusion. Indeed, the injected iodine accumulated in the injured tissue and led to a significant reduction in tissue damage.

While this work revealed iodine as a conserved part of a natural stress response in mammals, the Roth lab is motivated primarily by the promise it holds to save tissues, and lives, in a medical setting. “It might be used as a treatment in humans to improve outcome in situations involving extreme stress”, says Dr. Morrison. “If we learn more about [its function], can we develop a simple and safe method to preserve life?” The lab continues to explore iodine’s potential clinical applications, and perhaps this element will, someday soon, be doubly revered for its impacts on human health.

A hibernating arctic ground squirrel
The arctic ground squirrel releases iodine into its blood during hibernation. Dr. Mark Roth and colleagues believe this protects its tissues from low oxygen levels.

Morrison ML, Iwata A, Wick ML, VandenEkart E, Insko MA, Henning DJ, Frare C, Rice SA, Drew KL, Maier RV, Roth MB. Iodine Redistribution During Trauma, Sepsis, and Hibernation: An Evolutionarily Conserved Response to Severe Stress. Crit Care Explor. 2020 Sep 30;2(10):e0215. doi: 10.1097/CCE.0000000000000215.

This research was supported in part by grants from the Army Research Office (to Dr. Roth) and National Institutes of Health (to Dr. Drew).

Fred Hutch/UW Cancer Consortium member Mark Roth contributed to this work.