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By Will Boggs, MD

NEW YORK (Reuters Health) Mar 03 - Nicotinamide protects the developing mouse brain from some of the deleterious effects of ethanol, according to a report in the April issue of PLoS Medicine.

"As a psychiatrist and a neurologist, I commonly see young women with acute alcohol intoxication in the emergency room," Dr. Daniel G. Herrera from Weill Medical College of Cornell University, New York told Reuters Health. "It is possible that in those situations we could give nicotinamide and prevent damage to a developing baby."

Dr. Herrera and his colleague Dr. Alessandro Ieraci investigated whether the nutrient nicotinamide, an amide of vitamin B3, could prevent the neurotoxic effects of ethanol exposure in the postnatal brain of mice and analyzed whether inhibition of ethanol-induced apoptotic neuronal death could prevent behavioral impairment in adult mice. The brain-growth spurt that occurs in the 7-day postnatal period in mice correlates with neural development that takes place in the third trimester in humans.

Seven-day-old mice injected with ethanol showed a 15- to 20-fold increase of cleaved caspase-3 and widespread apoptotic neural cell death in the forebrain, the authors report. However, administration of nicotinamide significantly reduced caspase-3 activation.

Nicotinamide treatment 0, 2, 4, or 8 hours after ethanol administration prevented activation of caspase-3, with the strongest effect observed when nicotinamide was administered between 0 and 2 hours after ethanol exposure.

Nicotinamide treatment also significantly reduced the ethanol-induced increase in cytochrome-c release, the researchers note, but it did not alter the pharmacokinetics of ethanol.

Besides inhibiting ethanol-induced neuronal death, the report indicates, nicotinamide at the time of postnatal ethanol exposure prevented ethanol-induced behavioral impairments in adult mice.

"Although there are other studies showing a possible protective effect of antioxidants in preventing ethanol-induced apoptotic neuronal death, to our knowledge this is the first treatment that has been shown to work at the molecular, cellular, and behavioral levels," the authors conclude.

"The molecular mechanisms that we observe in ethanol exposure are common to other pathological contexts where cytochrome-c release is pivotal to initiate an apoptotic death cascade," Dr. Herrera explained. "Our hope is to be able to treat these conditions as well."

"I want to emphasize that fetal alcohol syndrome and fetal alcohol effects are preventable by not drinking alcohol," Dr. Herrera said. "Unfortunately, the reality is that women of fertile age continue to drink. The message is - do not drink -- while pregnant or possibly pregnant."

PLoS Medicine, 2006.