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

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."

add to favorites email to friend print save as pdf

Related Stories

Good housekeeping maintains a healthy liver

Oct 17, 2011

Differences in the levels of two key metabolic enzymes may explain why some people are more susceptible to liver damage, according to a study in the October 17 issue of the Journal of Cell Biology.

Recommended for you

Scientists discover gene controlling muscle fate

2 hours ago

Scientists at the University of New Mexico have moved a step closer to improving medical science through research involving muscle manipulation of fruit flies. They discovered in the flight muscles of Drosophila ...

Study clues to aging bone loss

2 hours ago

In Canada, bone fractures due to osteoporosis affect one in three women and one in five men over their lifetimes, costing the health care system more than $2.3 billion a year.

User comments