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（由申请人提供）：酒精消费是人类文明的千年组成部分。然而，酒精滥用或酒精中毒会引起一系列的器官功能紊乱，如大脑活动抑制、肝脏损害等，以及暴力、酒后驾车等社会问题，造成巨大的经济损失。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。在生物学上，酒精的代谢过程依赖于酒精脱氢酶（将乙醇转化为乙醛）和乙醛脱氢酶（将乙醛转化为乙酸）在辅酶-烟酰胺腺嘌呤二核苷酸（NADH）的帮助下的连续作用。然而，酶蛋白的稳定性和低细胞外NADH限制了这种脱氢酶作为细胞外抗酒精解毒剂的用途。为了规避这一限制，我们创建了稳定的酶纳米复合物，其由醇氧化酶和过氧化氢酶组成，醇氧化酶将醇氧化为乙醛，过氧化氢酶在不存在NADH的情况下从醇氧化中分解H2 O2。我们发现，乙醇氧化酶和过氧化氢酶的纳米胶囊在酒精中毒动物模型中有效地分解血液酒精。我们建议探索这种酶纳米胶囊作为解毒剂或解毒剂，酒精中毒或中毒。本研究拟合成含乙醇氧化酶、乙醛氧化酶和过氧化氢酶的功能性纳米胶囊，在体外和体内对乙醇进行完全分解，并评价其对乙醇分解、对酒精中毒动物的醒酒作用以及减轻酒精性肝损伤的效果。我们将通过酒精大剂量急性模型（暴饮）以及酒精喂养慢性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。