PITTSBURGH, Jan. 24 (UPI) -- A synthetic antioxidant delays and often prevents the onset of autoimmune or type 1 juvenile diabetes in mice, researchers reported Friday in the journal Diabetes.
"We've all heard a lot about how oxidative stress can damage cells and how we should take vitamins that work as antioxidants," co-author Jon Paganelli, formerly of the University of Colorado Health Sciences Center in Denver and now assistant professor of pediatrics at the University of Pittsburgh, told United Press International.
"The particular antioxidant we used in this study works very well at scavenging free radicals. The study showed the role that the generation of these particular free radicals has in causing some of the damage to cells important in making insulin. It is not the cause for all of the damage, but it plays a significant part," Paganelli said.
In autoimmune diabetes, the immune system misidentifies beta cells and attacks them. Inflammatory cells release free radicals that damage and kill the beta cells, eventually causing the body to make less insulin, leading to diabetes. Approximately 1 million people in the United States have type 1 diabetes and some 30,000 new cases are diagnosed each year.
The antioxidant used in the study protected beta cells from the free radicals mistakenly created and released destructively by the immune system. The antioxidant also blocked the ability of the immune system to recognize beta cells, the target of the autoimmune attack in diabetes.
"These data show that antioxidants protect against diabetes on two fronts. They not only mop up destructive oxygen radicals, but also alter the immune response," said co-author Dr. James Crapo, professor of medicine at National Jewish Medical and Research Center in Denver. "That suggests the intriguing possibility that we might one day treat a variety of autoimmune diseases by altering the oxidant/antioxidant balance of immune system."
"This study goes one step further than previous research in saying that free radicals are involved in killing beta cells. That's important," Dr. Scott Campbell, vice president of research programs at the American Diabetes Association in Alexandria, Va., told UPI. "And this research suggests the potential development of an alternative therapy to keep that from happening and preventing type 1 diabetes from developing."
The synthetic antioxidant, developed by Crapo and colleagues several years ago, is licensed by Incara Pharmaceuticals Corp. of Triangle Park, N.C. The compound, named AEOL 10113, imitates the action of the naturally occurring antioxidant superoxide dismutas, but is more potent and lasts longer in the body.
The researchers injected 10 mice with AEOL 10113 on the day before transplanting into them diabetes-causing T cells. After the transplants, they gave the mice the antioxidant four times, the last time on day 9. The five mice that did not get the antioxident all developed diabetes by day 13.
The mice treated with AEOL 10113 showed no signs of diabetes until day 21. Half were still diabetes-free at four weeks.
"We were surprised and pleased that the mice remained healthy for almost two weeks after the antioxidant treatments ended," Piganelli said. "That suggested to us that the antioxidant had altered the cells of the immune system."
Further experiments showed the antioxidant prevented the mouse immune system from recognizing certain antigens, molecules that trigger an immune response. This suggests the antioxidant might be useful in combination with other antigens to treat other autoimmune diseases.
Additional animal experiments are planned to prove the safety and potency of the antioxidant in animals before human trials are planned.
"Obviously we have a long way to go," Crapo said. "But we believe that these findings have opened a very promising new line of research."
The National Institutes of Health and the National Heart Lung and Blood Institute funded the research. Incara Pharmaceuticals provided the antioxidant.
(Reported by Bruce Sylvester from West Palm Beach, Fla.)
