Purdue researchers test drug to save cells after traumatic injury

WEST LAFAYETTE, IND. — Researchers at Purdue's School of Veterinary medicine have discovered the use of hydralazine can counteract the effects of acrolein after trauma.

Acrolein is a toxic byproduct that is produced as a result of nerve cell damage.

"Hydralazine relaxes the arteries and veins but is used traditionally as a hypertension drug in humans," says Dr. Riyi Shi, associate professor, lead researcher on the project. "What we found is the drug can keep more than 80 percent of cells alive after trauma, much like a beta blocker with high blood pressure."

Human trials to keep cells from dying were unsuccessful with previous studies conducted at the university, which encouraged the pursuit of an alternative method of cell repair.

"This is the most important discovery we have made at the Center for Paralysis Research – to date," Shi says. "We are testing the use of hydralazine in guinea pigs now in order to stave off the effects of spinal injuries or stroke. If the progress is promising with the guinea pigs, we will then test the drug on dogs and eventually humans."

Shi says he is hopeful that trials will approve this treatment for use in veterinary medicine.

"Dog spinal-cord problems, neurological diseases and oxidative stress issues are common," Shi adds. "Although the first generation of this drug probably won't be exactly what's used in an animal hospital or with people, this line of drug is likely to be seen helping veterinarians treat patients."

Acrolein was shown to kill groups of cells within a 12-hour time frame, according to Purdue officials. Hydralazine stops damage from reaching all cells. Using this drug to counteract the toxin is comparable to treating the problem instead of waiting to treat symptoms post-effect, Shi says.

How it works

Hydralazine binds to aldehydes, stopping deterioration of nerve fibers and neutralizing the toxicity and deactivating its potency. The toxin is then secreted by the body.

Researchers hope the drug can eventually be used to slow the effects of Alzheimer's and Parkinson's disease in people, providing a better quality of life.

"One side-effect that is unfavorable with the drug is that it lowers blood pressure," Shi says. "In cases of severe trauma, such as a dog hit by a car, the drug could not be used."

A similar drug based from hydralazine will have to be manufactured to eliminate this side-effect, or additional medication be required to reverse the blood pressure decrease, officials say.

The Purdue research findings were published in the Journal of Neuroscience Research in two articles. In one article, researchers discuss how acrolein kills cells, while the second article details the reversal of cell death after administration of hydralazine.

The research was sponsored by the National Institutes of Health, the state of Indiana and other federal funds.