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Scientists at the UA make critical end-stage liver disease discovery
Date:4/25/2014

A team of researchers in the University of Arizona's College of Pharmacy has discovered a molecular pathway that could be key to creating new therapeutics that would slow or even reverse the progression of end-stage liver disease.

Although cirrhosis of the liver is most commonly associated with alcohol or drug abuse, the condition marked by scar tissue replacing healthy liver tissue also can result from viral hepatitis, obesity and diabetes, as well as certain inherited diseases. According to the National Institutes of Health, cirrhosis is the 12th leading cause of death by disease in the U.S. As with many other human pathologic conditions, end-stage liver disease goes hand in hand with oxidative stress, which refers to damage inflicted to biological tissues by reactive oxygen molecules. Such molecules, also called free radicals, occur naturally as a byproduct of metabolic processes in the body and are associated with many chronic diseases including cancer, diabetes, neurodegenerative and cardiovascular diseases.

"Cells keep oxidative stress under control through various mechanisms," said Donna Zhang, a professor in the UA Department of Pharmacology and Toxicology, explaining that most of these mechanisms involve Nrf2, a protein present in virtually every cell that acts as a molecular switch. Nrf2 activates various biochemical mechanisms inside the cell that capture reactive oxygen molecules or dispose of damaged cellular components before they can cause more trouble. The antioxidants found in many fruits and vegetables exert their healthful benefits by capturing reactive oxygen molecules.

Under normal, healthy conditions, when no oxidative stress response is needed, an enzyme called Keap1 constantly chews up Nrf2, keeping its level low.

"Then, under stress from reactive oxygen molecules, or when you eat antioxidants from certain plants like broccoli sprouts, it prevents Keap1 from eating up Nrf2, allowing it to accumu
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Contact: Daniel Stolte
stolte@email.arizona.edu
520-626-4402
University of Arizona
Source:Eurekalert  

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