Oxidative stress and altered gene expression occurs in a metabolic liver disease model

October 30, 2012

A team of researchers under the direction of Dr. Jeffrey Teckman in the Department of Pediatrics at St. Louis University, have demonstrated that oxidative stress occurs in a genetic model of alpha-1-antitrypsin deficiency. This is the most common genetic liver disorder in children and can lead to cirrhosis and hepatocellular carcinoma in adults. Some cases may require liver transplantation. The report, published in the October 2012 issue of Experimental Biology and Medicine, suggests that treatment with antioxidants might be of therapeutic benefit for some individuals.

"We have evidence of oxidative stress in livers from an animal model that expresses the classical Z variant form of alpha-1-antitrypsin. The animal model recapitulates the human , in which the livers accumulate polymers of alpha-1-antitrypsin mutant Z protein, developing fibrosis and hepatocellular carcinoma with age", says Dr. Marcus. Potentially, non-invasive treatment involving long-term regulation of antioxidant levels could ameliorate the oxidative stress and retard the advancement of disease.

"This is an exciting new report which may help us understand the extreme variability between different patients with this same, single gene, metabolic liver disease. These findings may inform the pathophysiology of other liver diseases as well", says Dr. Teckman. In clinical studies, liver disease from alpha-1-antitrypsin mutant Z protein has shown considerable variability in severity and progression, suggesting that as yet undescribed genetic modifiers may influence disease development. Based on this study, certain involved in oxidative stress defense could be useful targets for further examination. Using microarray technology, the investigators have identified a number of potential alterations in gene expression pathways that could modify the development of liver pathologies. This information could be useful in defining genetic variants that may influence individual susceptibility and in facilitating the design of appropriate treatments.

Steven R. Goodman, PhD, Editor-in-Chief of said, "Teckman and colleagues have demonstrated that oxidative stress occurs in an animal model of Alpha-1-antitrypsin deficiency. This suggests that antioxidant treatment may be beneficial in this most common genetic liver disorder in children."

Explore further: New collaboration to develop treatments for liver disease

Related Stories

Molecular delivery truck serves gene therapy cocktail

August 15, 2011

In a kind of molecular gymnastics, scientists at the University of North Carolina at Chapel Hill School of Medicine have devised a gene therapy cocktail that has the potential to treat some inherited diseases associated with ...

Recommended for you

Key regulator of bone development identified

December 8, 2016

Loss of a key protein leads to defects in skeletal development including reduced bone density and a shortening of the fingers and toes—a condition known as brachydactyly. The discovery was made by researchers at Penn State ...

TET proteins drive early neurogenesis

December 7, 2016

The fate of stem cells is determined by series of choices that sequentially narrow their available options until stem cells' offspring have found their station and purpose in the body. Their decisions are guided in part by ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.