ALCOHOL-INDUCED LIVER DAMAGE: ROLE OF XANTHINE OXIDASE

酒精引起的肝损伤：黄嘌呤氧化酶的作用

• 批准号: 3445338
• 负责人: LESTER G SULTATOS
• 金额: $ 6.47万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1988-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3445338
• 关键词: alcoholism /alcohol abuse; allopurinol; drug adverse effect; drug metabolism; enzyme substrate; ethanol; hepatotoxin; hypoxanthines; liver ischemia /hypoxia; liver toxic disorder; superoxides; xanthine dehydrogenase; xanthine oxidase; xanthine oxidase inhibitor

The long term objective of this project is to supply information which will aid in the development of strategies for treatment and/or prophylaxis of ethanol-induced hepatotoxicity. It seeks to accomplish this objective by investigating a potential mechanism through which ethanol might exert its hepatotoxic effects. This research will focus on the elucidation of the effects of acute and chronic ethanol treatment on the hepatic xanthine dehydrogenase/oxidase system in rats. Both the potential conversion of xanthine dehydrogenase to the oxidase form of the enzyme and the accumulation of the substrate hypoxanthine as a result of ethanol-induced liver hypoxia could contribute markedly to liver damage through production of the highly toxic superoxide anion radical. If so, inhibition of xanthine oxidase by the drug allopurinol might diminish the hepatotoxic effects of ethanol. The specific aims of this proposal are as follows: 1. To determine if acute or chronic ethanol treatment causes the conversion of xanthine dehydrogenase to xanthine oxidase, as well as the accumulation of hypoxanthine in vivo, thereby triggering the production of the highly toxic superoxide anion radical. 2. To determine if effects of ethanol treatment on the hepatic xanthine dehydrogenase/oxidase system are responsible for the predisposition of ethanol treated animals to liver damage resulting from hypoxia. 3. To determine if inhibition of xanthine oxidase by the drug allopurinol can diminish ethanol-induced hepatotoxicity in rats subjected to brief hypoxia.

该项目的长期目标是提供信息 协助制定治疗和/或预防策略的制定 乙醇引起的肝毒性。 它试图通过 调查乙醇可能施加的潜在机制 肝毒性作用。 这项研究将重点阐明 急性和慢性乙醇治疗对肝黄嘌呤的影响 大鼠中的脱氢酶/氧化酶系统。 两者都是潜在的转换 黄嘌呤脱氢酶氧化酶形式的酶和酶形式 由于乙醇诱导的底物低黄嘌呤的积累 肝脏缺氧可以通过生产明显导致肝脏损害 高毒性的超氧化阴离子自由基。 如果是这样，抑制 药物素素醇的黄嘌呤氧化酶可能会减少肝毒性 乙醇的作用。 该提案的具体目的如下： 1。确定急性或慢性乙醇处理是否导致转化 黄嘌呤脱氢酶的黄嘌呤氧化酶以及积累 体内低黄嘌呤，从而触发高度的产生 有毒的超氧阴离子自由基。 2。确定乙醇的影响是否 肝黄嘌呤脱氢酶/氧化酶系统的治疗是 负责乙醇处理的动物对肝脏的倾向 缺氧导致的损害。 3。确定抑制黄嘌呤 氧化酶通过药物别嘌呤醇可减少乙醇诱导的肝毒性 在患有短暂缺氧的大鼠中。