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ETHANOL RESULTS IN OXIDANT DEPENDENT TISSUE INJURY

乙醇导致氧化依赖性组织损伤

基本信息

批准号：
6509262
负责人：
DALE A PARKS
金额：
$ 30.48万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-30 至 2004-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6509262
关键词：
ascorbate azo compounds enzyme activity ethanol glutathione high performance liquid chromatography laboratory mouse myoglobin nitrates nitric oxide nitric oxide synthase oxidative stress oxidized lipid peroxynitrites superoxides tocopherols

项目摘要

DESCRIPTION: (Adapted from the Investigator's Abstract) Chronic alcoholism is a major health problem in the U.S. resulting in over $12 billion dollars in medical expenses each year. Alcohol-induced hepatic damage is responsible for the majority of the morbidity and mortality associated with chronic alcohol consumption. Liver cirrhosis ranks as the 6th most common cause of death in the U.S., with ethanol implicated as the causative etiologic agent in 41-95 percent of the cases. The disease progresses from fatty infiltration and inflammation to irreversible tissue damage, with liver transplantation ultimately the only recourse. Although chronic alcohol consumption results primarily in hepatic dysfunction, there are also strong links to vascular (stroke, hypertension) and pulmonary (acute respiratory distress syndrome) complications. Chronic ethanol consumption has been linked to increased production of reactive oxygen and nitrogen species and compromised antioxidant defense systems. However, there are no studies which systematically integrate the effects of chronic ethanol consumption to the generation of reactive radical species, nitration of purines, proteins and lipids, and the consequent alterations in hepatic, pulmonary, and vascular structure/function. The investigators hypothesize that chronic ethanol administration increases nitric oxide ( NO), superoxide (02-), and peroxynitrite (ONOO-) production, thus leading to nitration and oxidation of biomolecules and compromised tissue structure/function. They propose to utilize genetically defined mouse models to modulate oxidant generating enzymes (iNOS and AO/XO) and antioxidant defenses (CuZn SOD1) to gain mechanistic insight into the ethanol-induced nitration of biomolecules and alterations in vascular and tissue structure/function. The investigators will ultimately apply targeted pharmacological interventions to minimize the ethanol-induced injury. Specific Aims: 1. Define the contribution of NO, O2-, and ONOO- in nitration of biomolecules (purines, proteins and lipids) and impaired tissue and vascular structure/function following chronic ethanol administration. 2. Modulate NO and 02- production to (a) reveal mechanisms of oxidative injury to liver, lung and vasculature, and (b) attenuate tissue and vascular dysfunction associated with chronic ethanol consumption. 3. Utilize targeted pharmacologic interventions to minimize chronic ethanol-induced nitration of biomolecules (purine, protein, and lipid) and subsequent impairment of tissue and vascular structure/function.These observations will provide a foundation for understanding the interactions for understanding the interactions of superoxide with NO in hepatic, pulmonary, and vascular tissue injury resulting from chronic ethanol administration. Mechanistic insights gained from these studies will guide development of pharmacologic interventions to limit the detrimental effects of reactive species and decrease the morbidity and mortality associated with chronic alcohol consumption and serve as a prelude to human clinical trials.

描述：（改编自研究者摘要）慢性酒精中毒

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Dietary flavonoid quercetin stimulates vasorelaxation in aortic vessels.

DOI：
10.1016/j.freeradbiomed.2010.04.022
发表时间：
2010-08-01
期刊：
FREE RADICAL BIOLOGY AND MEDICINE
影响因子：
7.4
作者：
Khoo, Nicholas K. H.;White, C. Roger;Pozzo-Miller, Lucas;Zhou, Fen;Constance, Chad;Inoue, Takafumi;Patel, Rakesh P.;Parks, Dale A.
通讯作者：
Parks, Dale A.

Peroxynitrite decreases hemostasis in human plasma in vitro.

过氧亚硝酸盐会降低体外人血浆中的止血作用。