Alcohol consumption is a millennium-old component of human civilization. Alcohol abuse or alcohol intoxication, however, associates with a series of organ disorders such as depressing brain activities and damaging the liver and social problems such as violence and driving under alcohol influence (DUI), resulting in huge economic loss. A direct way to reduce blood alcohol level immediately after alcohol consumption is not available. Biologically, metabolic process of alcohol relies on consecutive actions of alcohol dehydrogenase (conversion of ethanol to acetaldehyde) and acetaldehyde dehydrogenases (conversion of acetaldehyde to acetic acid) with the help of co-enzyme-nicotinamide adenine dinucleotide (NADH). However, both enzyme protein stability and low extracellular NADH restricts the use of such dehydrogenases as extracellular antidotes against alcohol. To circumvent this limitation, we created stable enzyme nanocomplexes composed of alcohol oxidase that oxidizes alcohol to acetaldehyde and catalase that decomposes H2O2 from the alcohol oxidation in the absence of NADH. We found that the nanocapsules of alcohol oxidase and catalase effectively decomposed blood alcohol in alcohol intoxicated animal models. We propose to explore such enzyme nanocapsules as antidotes or prophylactics to alcohol intoxication or poisoning. We will synthesize functional enzyme nanocapsules containing alcohol oxidase, acetaldehyde oxidase and catalase for a complete in vitro and in vivo alcohol decomposition, and evaluate efficacy of the enzyme nanocapsules in decomposing alcohol and sobering up alcohol intoxicated animals or reducing alcohol-induced liver injury. We will accomplish our aims with acute model of alcohol boluses (binge drinking) as well as with chronic model of alcohol feeding. Successful completion of this exploratory study will pave the way for clinical trials for effective alcohol antidotes.
NIH ExPorter
NIH ExPorter