[英语，新闻] Antioxidant may prevent alcohol-induced liver disease

StephenW

Antioxidant may prevent alcohol-induced liver diseasePublished: Monday, May 2, 2011 - 16:35 in Health & Medicine
      An antioxidant may prevent damage to the liver caused by excessive alcohol, according to new research from the University of Alabama at Birmingham. The findings, published online April 21, 2011, in the journal Hepatology, may point the way to treatments to reverse steatosis, or fatty deposits in the liver that can lead to cirrhosis and cancer. The research team, led by Victor Darley-Usmar, Ph.D., professor of pathology at UAB, introduced an antioxidant called mitochondria-targeted ubiquinone, or MitoQ, to the mitochondria of rats that were given alcohol every day for five to six weeks in an amount sufficient to mirror excessive intake in a human.
Chronic alcoholics, those who drink to excess every day, experience a buildup of fat in the liver cells. When alcohol is metabolized in the liver, it creates free radicals that damage mitochondria in the liver cells and prevent them from using sufficient amounts of oxygen to produce energy. Moreover, the low-oxygen condition called hypoxia worsens mitochondrial damage and promotes the formation of the fatty deposits that can progress to cirrhosis.
Darley-Usmar and his collaborators say that the antioxidant MitoQ is able to intercept and neutralize free radicals before they can damage the mitochondria, preventing the cascade of effects that ultimately leads to steatosis.
"There has not been a promising pharmaceutical approach to preventing or reversing the long-term damage associated with fatty deposits in the liver that result from excessive consumption of alcohol," said Darley-Usmar. "Our findings suggest that MitoQ might be a useful agent for treating the liver damage caused by prolonged, habitual alcohol use."
&quotrevious studies have shown that MitoQ can be safely administered long-term to humans," said Balu Chacko, Ph.D., a research associate and co-author of the study. "As it has been shown to decrease liver damage in hepatitis C patients, it may have potential to ameliorate the initial stages of fatty liver disease in patients with alcoholic and non-alcoholic liver disease."
The Annals of Hepatology estimate that alcohol abuse costs $185 billion annually in the United States, and that 2 million people have some form of alcoholic liver disease.  It links as much as 90 percent of cirrhosis of the liver is related to alcohol abuse and up to 30 percent of liver cancer.
Darley-Usmar, who is also the director of the Center for Free Radical Biology at UAB, says his team is in discussions with the National Institutes of Health to develop a whole family of drugs based around interactions with mitochondria.  He suggests such drugs might be effective in treating cardiovascular disease, kidney disease and neurodegenerative disorders.
"We know that free radicals play a role in human disease, and we have developed antioxidants that can eliminate free radicals in the laboratory," he said. "Unfortunately, previous trials using antioxidants in humans have not been as successful as anticipated. The difference with our current findings is that we targeted a specific part of the cell, the mitochondria.  This is a unique approach, and this is one of the few pre-clinical trials that shows effectiveness."
Darley-Usmar says the findings also may have significance for the treatment of metabolic syndrome, a rapidly growing condition that affects some 50 million Americans, according to the American Heart Association.
"Metabolic syndrome describes a complex interaction of factors caused by obesity which includes damage to the liver due to an increase in free radicals, hypoxia and deposition of fat," said Darley-Usmar.  "It's quite similar to alcohol-dependent hepatotoxicity. It would be interesting to see if an antioxidant such as MitoQ had any therapeutic effect in preventing liver damage in those with metabolic syndrome."
  Source: University of Alabama at Birmingham



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StephenW

抗氧化剂可以预防酒精性肝病
发布时间：星期一，2011年5月2日 - 16:35健康与医学

一种抗氧化剂可以防止过度破坏所造成的酒精肝，据来自伯明翰阿拉巴马大学的新研究。这项研究结果在网上公布2011年4月21日在杂志，肝脏，可能指向的方式处理，以扭转脂肪变性，或在肝脏，可导致肝硬化和癌症的脂肪堆积。该研究小组由Victor达利- Usmar，博士，病理学教授UAB的领导介绍了一种抗氧化剂称为线粒体定位的辅酶，或对大鼠线粒体被给予酒精MitoQ，每五到六个星期日其数额足以反映在一个人摄入过多。

慢性酗酒，谁喝过量的每一天，体验到一种脂肪在肝细胞堆积。当酒精在肝脏代谢，它创建的自由基损伤肝细胞线粒体和防止使用足量的氧气产生能量他们。此外，低氧条件下缺氧恶化称为线粒体损伤和促进脂肪沉积，可进展为肝硬化的形成。

达利- Usmar和他的合作者说，抗氧化剂MitoQ能够拦截，中和自由基，才可以破坏线粒体，防止影响，最终导致脂肪变性级联。

“有没有一个充满希望的制药方法来阻止或扭转长期损害相关的脂肪在肝脏沉积，从过度消费酒精的结果，”达利说，Usmar。 “我们的研究结果表明，MitoQ可能是治疗肝损伤的长期，习惯性使用酒精引起的有用的代理人。”

“以前的研究表明，MitoQ可以安全管理的长期给人类，说：”巴鲁Chacko，博士，副研究员和合作研究报告的作者。 “由于它已被证明是减少丙型肝炎患者肝损害，可能有潜力改善酒精性和非酒精性脂肪肝病患者的肝脏疾病的初期阶段。”

肝脏病的志估计，酗酒成本1850亿美元，每年在美国，并有200万人口有一定的酒精性肝病的形式。它连结多达90百分之肝硬化与酒精滥用和高达百分之30的肝癌。

达利- Usmar，谁也是在UAB的自由基生物学中心主任，说他的团队在与美国国立卫生研究院的讨论是建立一个与线粒体周围的药物相互作用的整个家庭。他建议这些药物可能对治疗心血管疾病，肾脏疾病和神经退行性疾病有效。

“我们知道，自由基在人类疾病发挥作用，我们已经开发的抗氧化剂，可以消除自由基的实验室，”他说。 “不幸的是，以前使用的抗氧化剂在人体试验尚未如预期的那样成功。与我们的目前的研究结果不同的是，我们针对一个特定部分的细胞中，线粒体。这是一种独特的方法，这是少数人临床前试验显示成效。“

达利- Usmar说，调查结果也可能对代谢症候群的一个快速增长的条件，影响到大约5000万美国人治疗的意义，根据美国心脏协会。

“代谢症候群描述了肥胖，其中包括对肝脏的损害是由于自由基，缺氧，造成脂肪沉积增加复杂因素的相互作用，”达利说，Usmar。 “这是非常相似，酒精依赖的肝毒性。这将是有趣的，看看是否有抗氧化剂，如MitoQ任何预防代谢综合征的肝脏损伤的治疗作用。”
来源：亚拉巴马大学伯明翰