An investigational compound may help metabolize acetaldehyde for people with impaired ability to detoxify, a study supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has shown. Findings from the study are published in the Proceedings of the National Academy of Sciences (PNAS).

Researchers have developed small molecules called aldehyde dehydrogenase activators, (Aldas) that have previously been found to increase activity of aldehyde dehydrogenase 2 (ALDH2), the main enzyme that breaks down acetaldehyde into acetate. Acetaldehyde is a toxic chemical metabolite that results when alcohol is consumed.

In the study, a new compound called Alda-89, was found to provide another enzyme ALDH3A1 with increased acetaldehyde-metabolizing abilities that it normally does not have. Researchers posed that by involving ALDH3A1 to also metabolize acetaldehyde, it could speed up the acetaldehyde elimination from tissues that are more prone to its harmful effects.

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Researchers were able to demonstrate that Alda-89 increased acetaldehyde metabolism in both normal mice and mice with the ALDH2 mutation found in the East Asians. When Alda-89 was combined with Alda-1 (previously shown to activate ALDH2), elimination of acetaldehyde was faster than activating each ALDH alone. Further, mice treated with Alda-89 plus Alda-1 showed faster recovery from alcohol intoxication. Findings from this study may lead to new treatments to help those with impaired ability to break down acetaldehyde and other toxic substances.

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