FREE RADICALS IN ALCOHOLIC LIVER INJURY

肝硬变是一种严重的病理表现。 酗酒。尽管乙醇对肝脏各方面的影响 功能已被广泛研究，酗酒的具体原因 肝病并不为人所知。一种拟议的机制是免费的 酒精暴露后可能会产生自由基。乙醇已经被证明 被代谢成自由基中间体1-羟乙基 乙醇处理后，检测到自由基和脂质自由基 使用自旋捕获技术对实验动物进行管理。 这项提议所基于的工作假设是 1-羟乙基引发细胞内自由基级联 最终导致脂自由基、脂类形成的反应 过氧化，以及酒精滥用的其他毒性表现。 科学文献表明，氧自由基可能具有 在酒精性肝病发展中的作用和结果 在目前的项目中已经证明了羟基自由基具有 乙醇在肝脏羟乙基自由基代谢中的作用 微粒体。这项研究将探索导致疾病的机制。 乙醇和氧的自由基中间体的形成， 尤其是羟基自由基的起源，经过急性或长期 酒精管理。营养、生理和药理 可能促进或拮抗酒精诱导的游离的干预 激进的一代将被描述为。最后，生理学的 激进分子的后果将通过评估 肝脏在某些条件下的生化变化会加剧 这些高活性中间体的生成。 这项研究的长期目标是利用自旋陷阱。 评估自由基在酒精损伤中的作用的技术。 这些信息应该有助于开发方法来 将未获得控制的个体的肝脏损伤降至最低 因为他们有酗酒的冲动。改进的治疗方法可以 这也是本研究的结果。在更广泛的范围内，自由基是 被认为在许多不同类型的病理性疾病中起作用 条件，以便更好地了解它们在促进 组织损伤应提供其他健康所需的基本信息 有问题。

Cirrhosis of the liver is a serious pathological manifestation of alcohol abuse. Although effects of ethanol on various aspects of hepatic function have been studied extensively, the specific causes of alcoholic liver disease are not understood. One proposed mechanism is that free radicals may be generated after ethanol exposure. Ethanol has been shown to be metabolized to a free radical intermediate, the 1-hydroxyethyl radical, and lipid radicals have been detected after ethanol administration to experimental animals, using spin trapping techniques. The working hypothesis upon which this proposal is based is that the 1-hydroxyethyl radical initiates a cascade of cellular free radical reactions which ultimately lead to the formation of lipid radicals, lipid peroxidation, and other toxic manifestations of ethanol abuse. The scientific literature indicates that oxygen radicals may have a role in the development of alcoholic liver disease, and results obtained during the current project have proven that the hydroxyl radical has a role in the metabolism of ethanol to the 1hydroxyethyl radical in liver microsomes. This research will probe mechanisms which lead to the formation of free radical intermediates of ethanol and oxygen, particularly the origin of the hydroxyl radical, after acute or long-term alcohol administration. Nutritional, physiological, and pharmacological interventions which may promote, or antagonize, alcohol-induced free radical generation will be characterized. Finally, the physiological consequences of the radicals will be investigated by assessing biochemical changes in the liver under conditions found to intensify the generation of these highly reactive intermediates. The long-term goal of this research is to utilize spin trapping. techniques to evaluate the roles of free radicals in alcoholic injury. This information should be useful for the development of methods to minimize liver injury in those individuals who have not gained control over their compulsion to abuse alcohol. Improved treatment methods may also result from this research. On a broader scale, free radicals are thought to have a role in many different types of pathological conditions, so that a better understanding of their role in promoting tissue injury should provide basic information needed for other health problems.