Nanocapsules that decompose alcohol as antidotes for alcohol intoxication.

分解酒精的纳米胶囊作为酒精中毒的解毒剂。

• 批准号: 8874057
• 负责人: CHENG JI
• 金额: $ 26.75万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8874057
• 关键词: Accident and Emergency department; Acetaldehyde; Acetates; Acetic Acids; Acute; Alanine Transaminase; Alcohol abuse; Alcohol consumption; Alcohol dehydrogenase; Alcohol-Induced Disorders; Alcoholic Intoxication; Alcoholic Liver Diseases; Alcohols; Animal Model; Animals; Antidotes; Automobile Driving; Binding; Blood; Blood alcohol level measurement; Bolus Infusion; Brain; CYP2E1 gene; Chemical Engineering; Chronic; Civilization; Clinical Trials; Cytochromes; Depressed mood; Diet; Disease; Drug Kinetics; Drug Metabolic Detoxication; Economics; Encapsulated; Enzymes; Ethanol; Felis catus; Hour; Human; Hydrogen Peroxide; In Vitro; Injury; Intestines; Liquid substance; Metabolism; Modeling; Molecular; Monitor; Multienzyme Complexes; Mus; NADH; Neurons; Nicotinamide adenine dinucleotide; Organ; Oxidases; Oxidoreductase; Poisoning; Polymers; Preventive; Proteins; Series; Social Problems; Surface; Testing; Therapeutic; Time; Tissues; Toxic effect; Violence; Water; acetaldehyde dehydrogenase; alcohol oxidase; alcohol poisoning; base; binge drinking; catalase; effective therapy; extracellular; feeding; health economics; immunogenicity; improved; in vivo; liver injury; nanocapsule; nanoscale; oxidation; prophylactic; public health relevance; receptor; sobriety

 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.

 描述（申请人提供）：饮酒是人类文明的一个千年组成部分，然而，酗酒或酒精中毒会导致一系列器官疾病，如抑制大脑活动、损害肝脏以及暴力和暴力等社会问题。酒后驾驶（DUI），造成巨大的经济损失，目前还没有一种直接的方法可以在饮酒后立即降低血液中的酒精含量。从生物学角度来说，酒精的代谢过程依赖于乙醇脱氢酶的连续作用。然而，酶蛋白稳定性和低细胞外 NADH 限制了此类脱氢酶作为细胞外解毒剂的使用。为了规避这一限制，我们创建了由酒精氧化酶组成的稳定酶纳米复合物，将酒精氧化为乙醛和过氧化氢酶，在没有 NADH 的情况下将酒精氧化产生的 H2O2 分解。我们发现，乙醇氧化酶和过氧化氢酶的纳米胶囊可以有效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解毒剂或预防剂。我们将合成含有酒精的功能性纳米胶囊。氧化酶、乙醛氧化酶和过氧化氢酶在体外和体内完全分解酒精，并评估酶纳米胶囊在分解酒精和清醒酒精中毒动物或减少​​酒精引起的肝损伤方面的功效，我们将通过急性模型来实现我们的目标。酒精丸（暴饮）以及慢性酒精喂养模型的成功完成这项探索性研究将为有效酒精的临床试验铺平道路。解毒剂。