The new research found a 36 percent reduction in limb malformations in the offspring of pregnant mice exposed to ethanol and at the same time given a newly developed antioxidant compound called EUK-134.
The study appears on-line Friday (June 18) in FASEB-J, the journal of the Federation of American Societies for Experimental Biology.
"What makes this study unique is that it shows for the first time that giving antioxidants to a pregnant mother at the same time she's exposed to alcohol can diminish the incidence of major malformations," said Dr. Kathleen K. Sulik, professor of cell and developmental biology at UNC's School of Medicine.
Antioxidants protect key cellular components by neutralizing the damaging effects of free radicals, natural byproducts of cell metabolism. Free radicals form when oxygen is metabolized, or burned off, by the body. They travel through cells, disrupting the structure of other molecules, causing cellular damage. Such cell damage is believed to contribute to aging and various health problems. Examples of antioxidants are selenium, vitamin C and E, zinc and superoxide dismutase (or SOD), a zinc- and copper- or manganese-containing enzyme that reacts with superoxide radicals to convert them to less dangerous chemical entities.
Dietary antioxidants have attracted considerable interest in the popular press as potential treatments for cancer, atherosclerosis, chronic inflammatory disease and aging.
Sulik, a member of the university's Bowles Center for Alcohol Studies, said a major focus of her research has been cellular mechanisms involved in birth defect formation, particularly those linked to ethanol exposure, such as fetal alcohol spectrum disorders, or FASD. Until now, much of this research at UNC and elsewhere has involved growing cells in the laboratory.
"We have used embryonic neural crest cells, which are very sensitive to ethanol," said Dr. Shao-yu Chen, a member of the Bowles Center for Alcohol Studies, assistant professor of cell and developmental biology and lead author of the new report.
"In a cell culture system, ethanol induces the death of these cells. But when we place antioxidants into the culture together with ethanol, the cells are protected from cell death." Chen also has shown that ethanol-induced cell death is related to free radical generation. "We have used superoxide dismutase and vitamin E and found that in the presence of ethanol both agents reduce free radical production," he said.
Chen and Sulik have extended their cell culture research to a whole embryo culture system. In this technique, early mouse embryos are grown in the laboratory and exposed to various levels of ethanol and antioxidants. Embryos are then monitored for evidence of cell death and abnormal development. "Using this method, we also showed that SOD can diminish ethanol-induced cell death and subsequent malformations," Chen said.
As to the new study, Sulik said, the implications apply directly to people with alcoholism. "The nutritional status of alcoholics isn't the best. People who are alcoholic by definition can't control their drinking and often cannot quit drinking during pregnancy.
"And so the practical point of this paper is that perhaps we can diminish some of the problems that might exist if the nutritional status of alcoholic mothers improves. It would be great if these women would supplement their diets with a daily multivitamin."
However, just like alcohol, even too many vitamins (especially vitamin A) can be harmful to a fetus, Sulik said. "The idea of possibly adding antioxidants to alcoholic beverages has been proposed as a way of helping the situation, at least a little, for those women who are unable to quit drinking alcohol."
The amount of alcohol used in the study is high, Sulik added, equivalent to the amount that would raise the blood alcohol level of a person up to 0.4 or 0.5. This is a level that can be achieved by chronic alcoholics, people who have acquired a tolerance for alcohol. "Virtually all children born with full-blown fetal alcohol syndrome, with major malformations caused by alcohol, are born to chronic alcoholics," Sulik said. "Chronic alcoholism is a huge problem in our population."
Results from the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a study directed by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), show that the number of American adults age 18 years and older who abuse alcohol or are alcohol dependent rose from 13.8 million (7.41 percent) in 1991-1992 to 17.6 million (8.46 percent) in 2001-2002.
"There is no 'magic number' as to a safe versus unsafe amounts of alcohol consumed during pregnancy," Sulik said. "It would differ from person to person. It would be different depending on the stage of pregnancy, the sensitivity of the developing fetus.
"And the stages we're looking at are really very early, before women would even recognize pregnancy. The bottom line: If there's a chance you could become pregnant, don't drink, or if you're drinking don't get pregnant."
The research was supported by grants from the National Institute on Alcohol Abuse and Alcoholism. "This is an elegant expansion of Dr. Sulik and other researchers' work that further strengthens our understanding of the oxidative processes involved in the development of fetal alcohol spectrum disorders. This finding may contribute to a new approach in preventing FASD," said Dr. Kenneth Warren, the institute's associate director.
By Leslie H. Lang
UNC School of Medicine