Antioxidants May Alleviate Brain Dysfunction Often Seen with Chronic Kidney Failure

http://www.uadv.uci.edu:300/releases/135ap01.html

135-AP-01

FOR IMMEDIATE RELEASE

ANTIOXIDANTS MAY ALLEVIATE BRAIN DYSFUNCTION OFTEN SEEN WITH CHRONIC KIDNEY FAILURE

Study Finds Free Radicals, Nitric Oxide May Have Role in Frequent Complication for Dialysis Patients

Irvine, Calif., Sept. 19, 2001 -- Certain powerful antioxidants may successfully treat the impaired neurological functions seen in patients with chronic kidney failure, a UC Irvine College of Medicine study has found.

The study, conducted in rats, shows for the first time how a group of molecules known as free radicals interacting with another molecule called nitric oxide can contribute to the neurological problems that often occur with kidney failure. The study appears in the September issue of the Journal of the American Society of Nephrology.

Kidney failure is considered one of the most serious chronic disorders in the United States. More than 300,000 people are treated for it annually, a number that has doubled since 1989, according to the U.S. Renal Data Survey, a division of the U.S. Public Health Service. It is caused usually by diabetes, untreated high blood pressure, inflammation of the kidneys, inherited disorders and infections.

Currently, there is no cure; dialysis and kidney transplants are used to extend the lives of kidney failure patients. Every year, chronic kidney failure has forced about 200,000 people to be on dialysis and about 87,000 people to have a kidney transplant. These treatments, however, do not improve the wide variety of neurological complications that are common in kidney failure.

"It's been documented that kidney failure patients suffer from neurological complications, but the precise reason for the complications isn't known," said Dr. Nick Vaziri, professor of medicine and lead researcher of the study. "This study shows how free radicals and nitric oxide interact to produce oxidative stress and help cause these neurological dysfunctions. It also may provide a way to treat these disorders."

Vaziri and his colleagues found that rats with most of their kidneys removed to simulate chronic kidney failure had higher levels of a chemical that indicated an increase in free radicals. These molecules are known to damage cells through a process called oxidative stress. Evidence of oxidative stress was found in areas of the cerebral cortex and could be reduced by treatment with a powerful antioxidant.

The team found that nitric oxide, which helps maintain normal blood pressure but also acts as an important signaler of messages between and within cells, interacts with reactive oxygen species (often known as free radicals) to cause brain cell damage during kidney failure. This interaction between nitric oxide and free radicals produces more cell-damaging molecules. These molecules can lead to brain dysfunctions by damaging cells there.

By treating the rats with kidney failure with an antioxidant called des-methyl-tirilizad, the researchers found much lower levels of the molecules that lead to oxidative stress and brain damage.

Neurological disorders seen in kidney failure patients include slowed thought processes, fatigue, apathy, emotional instability, sleep disorders, hormone imbalance, forgetfulness, agitation and, in severe cases, delirium, hallucinations, coma and convulsions.

"This study points to the role of oxidative stress and nitric oxide in the development of brain dysfunction in kidney failure," Vaziri said. "We may be able to link these results with similar events that occur in the nervous system in other disorders, such as Huntington's disease, Alzheimer's disease, brain injury and carbon monoxide poisoning. However, more studies are needed to determine if this could be useful to humans."

Vaziri's team has worked for many years in attempting to determine how nitric oxide and antioxidants interact in a number of disorders, including high blood pressure and kidney disease.

Vaziri's colleagues included Gangmin Deng, Zhemin Ni and Xiao-Xin Yan of UCI and Bahman Jabbari of the Uniformed Services University in Bethesda, Md.

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Contact:Andrew Porterfield(949) 824-3969[email protected]

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