Drug That Binds Iron Could Be a Godsend For Stubborn Limb Wounds
Deferoxamine, a drug already FDA-approved for the treatment of disorders related to excess iron in the blood, may help doctors heal stubborn leg and foot wounds in people with diabetes. Scientists at the Stanford University School of Medicine and the Albert Einstein College of Medicine found that with deferoxamine, small cuts in diabetic mice healed 10 days faster than they did in untreated mice: 13 days as opposed to 23 days. If deferoxamine works similarly on humans, it could significantly speed the healing of diabetic wounds.
Diabetic wounds heal slowly because the body doesn't do a good job of creating new blood vessels to reconnect the damaged tissue to the oxygen-bearing bloodstream. Previously, scientists didn't know why these new connections didn't take place. Now, based on the Stanford/Einstein study, they believe that the high-glucose environment of diabetic tissue prevents the production of a necessary vessel-building factor known as VEGF.
VEGF, or vascular endothelial growth factor, is a protein that prompts new blood vessel formation. Fibroblasts, the cells that heal wounds, ramp up the production of VEGF when oxygen levels drop. To study how this was going wrong in diabetic tissue, the researchers grew some fibroblasts in high-glucose environments and others in low-glucose environments. The low-glucose fibroblasts increased VEGF production by 200 percent, versus only 20 percent in the high-glucose group. And mice treated with deferoxamine produced almost threefold more VEGF than untreated mice.
The researchers found that glucose interferes with the production of VEGF by creating free radicals, which oxidize iron. The oxidized iron interacts with other molecules to form hydroxyl radicals, which then damage DNA.
For the production of VEGF to occur, two things must happen. First, DNA must bind with a protein called HIF-1a, a sort of cellular sensor that sounds an alert when oxygen is low. That interaction allows the DNA to produce the growth factor, which then allows the creation of new blood vessels.
But to work efficiently, HIF-1a also needs to bind with a molecule called p300. In high-glucose environments, HIF-1a binds with p300 only half as well as normal. The result is a drastic reduction in fibroblasts' ability to heal damaged tissue.
Because deferoxamine binds to and removes iron from cells, the Stanford/Einstein researchers hypothesized that it could prevent the DNA damage that ultimately resulted from the oxidized iron that is created in a high-glucose environment. And in fact, the drug did bring the binding of p300 and HIF-1a back to normal levels.
Scientists are already experimenting with ways to use deferoxamine in the treatment of diabetic wounds. Although the drug is commonly injected when used for iron overload, the Stanford/Einstein team is developing a dissolvable sheet that could be placed directly on a wound to deliver deferoxamine as a medication.Click Here To View Or Post Comments