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Transcription factor may protect against hepatic injury caused by hepatitis C and alcohol
Date:11/10/2013

Philadelphia, PA, November 11, 2013 New data suggest that the transcription factor FOXO3 may protect against alcohol-induced liver injury. Researchers determined that alcohol given to mice deficient in FOXO3 caused severe liver injury resembling human alcoholic hepatitis. Further they found that although hepatitis C virus (HCV) and alcohol independently activated FOXO3, in combination they suppressed FOXO3, reduced expression of cytoprotective genes, and worsened liver injury. The results are published in The American Journal of Pathology.

"There is emerging evidence that the FOXO transcription factor family plays a critical role in metabolic, antioxidant, and cell death responses in the liver. The role of FOXO in injury processes is complex as FOXO transcription programs can either be cytoprotective or cytotoxic, and well-documented examples of both phenomena are numerous," says Steven A. Weinman, MD, PhD, Department of Internal Medicine at the University of Kansas Medical Center.

Based on such emerging evidence, Dr. Weinman's group fed alcohol to FOXO3-deficient mice for three weeks. One third of these mice developed severe hepatic steatosis (infiltration of liver cells with fat), neutrophil infiltration, and necrosis, similar to that seen in patients with alcoholic hepatitis. In some mice, levels of the liver enzyme alanine aminotransferase (ALT) increased tenfold compared to controls.

Investigators also induced severe liver injury with alcohol in a mouse model of HCV (transgenic HCV/Sod2+/-). These animals had elevated ALT; increased ICAM-1 expression and caspase 3 cleavage, and severe steatosis, lobular inflammation, and ballooning degeneration of liver cells. In these mice, degree of liver injury correlated with levels of the mitochondrial antioxidant enzyme superoxide dismutase (SOD2). (SOD2 is also thought to play a part in protecting the liver from alcoholic injury.) Alcohol-treated HCV/Sod2+/- mice also showed a
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Contact: Eileen Leahy
ajpmedia@elsevier.com
732-238-3628
Elsevier Health Sciences
Source:Eurekalert

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