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."
"Previous 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."
Primary collaborators on the study are Michael P. Murphy, Ph.D., MRC Mitochondrial Biology Unit, Cambridge, UK and Balaraman Kalyanaraman, Ph.D., University of Wisconsin. The research group at UAB included Anup Srivastava, Ph.D., Michelle Johnson, Gloria Benavides, Ph.D., Yaozu Ye, M.D., Nirag Jhala, Mi Jung Chang. Funding for the study came from the National Institutes of Health.
Known for its innovative and interdisciplinary approach to education at both the graduate and undergraduate levels, the University of Alabama at Birmingham is the state of Alabama's largest employer and an internationally renowned research university and academic health center; its professional schools and specialty patient-care programs are consistently ranked among the nation's top 50. Find more information at www.uab.edu and www.uabmedicine.org.
EDITOR'S NOTE: The University of Alabama at Birmingham (UAB) is a separate, independent institution from the University of Alabama, which is located in Tuscaloosa. Please use University of Alabama at Birmingham on first reference and UAB on second reference.
VIDEO: www.youtube.com/uabnews TEXT: www.uab.edu/news TWEETS: www.twitter.com/uabnews
Bob Shepard | EurekAlert!
Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin
Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care
The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.
The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
29.05.2017 | Earth Sciences
29.05.2017 | Life Sciences
29.05.2017 | Physics and Astronomy