Nanocapsules that decompose alcohol as antidotes for alcohol intoxication.

 描述(申请人提供)：酒精消费是人类文明的千年组成部分。然而，酗酒或酒精中毒会导致一系列器官障碍，如抑制大脑活动和损害肝脏，以及暴力和酒后驾车(DUI)等社会问题，导致巨大的经济损失。在饮酒后立即降低血液酒精水平的直接方法是不可用的。在生物学上，酒精的代谢过程依赖于辅酶-烟酰胺腺嘌呤二核苷酸(NADH)的乙醇脱氢酶(乙醇转化为乙醛)和乙醛脱氢酶(乙醛转化为乙酸)的连续作用。然而，酶蛋白的稳定性和胞外NADH的低水平限制了这类脱氢酶作为胞外酒精解毒剂的使用。为了克服这一限制，我们创造了稳定的酶纳米复合体，它由将乙醇氧化为乙醛的酒精氧化酶和在没有NADH的情况下分解乙醇氧化产生的过氧化氢的过氧化氢酶组成。我们发现乙醇氧化酶和过氧化氢酶纳米胶囊能有效地分解酒精中毒动物模型中的血液酒精。我们建议探索这种酶纳米胶囊作为酒精中毒或中毒的解毒剂或预防性药物。我们将合成含有乙醇氧化酶、乙醛氧化酶和过氧化氢酶的功能酶纳米胶囊，用于在体外和体内完全分解酒精，并评价该酶纳米胶囊对酒精中毒动物的分解和醒酒或减轻酒精所致肝损伤的效果。我们将通过急性饮酒模型(酗酒)和慢性酒精喂养模型来实现我们的目标。这项探索性研究的成功完成将为有效的酒精解毒剂的临床试验铺平道路。

 DESCRIPTION (provided by applicant): 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.