The results of this study appear in the March 2005 issue of Liver Transplantation, the official journal of the American Association for the Study of Liver Diseases (AASLD) and the International Liver Transplantation Society (ILTS). The journal is published on behalf of the societies by John Wiley & Sons, Inc. and is available online via Wiley InterScience at http://www.
Approximately one-fifth of the U.S. population is afflicted with hepatic steatosis due to a rising incidence of obesity. Because fatty livers are more sensitive than lean livers to I/R injury and are associated with an increased risk of disease and death, this has resulted in fewer usable donors for liver transplants. In fact, nearly one-third of all donated livers are afflicted with fatty changes, but longer waiting lists are forcing practitioners to consider using these organs. A previous study found that rinsing livers with a solution containing green tea extract prevented failures in transplants using fatty livers. The current study examined whether (-)-epigallocatechin-3-gallate (EGCG), the major flavonoid component found in green tea, protected fatty livers from cell damage after I/R injury.
Led by Kenneth D. Chavin, M.D., Ph.D., of the Medical University of South Carolina in Charleston, SC, researchers administered EGCG either orally or by injection and performed surgery to induce I/R injury in mice; control groups did not receive the EGCG. Mice receiving EGCG by either method showed a survival rate of 100 percent, versus 65 percent for the controls. Tissue analysis showed that the EGCG mice had decreased necrosis (cell death) and a higher percentage of viable tissue, demonstrating that the flavonoid protected the liver from I/R injury.
The next step was to determine the mechanism by which EGCG protected fatty liver cells from I/R injury. Researchers developed a technique to measure fatty acids and found that levels of palmitic and linoleic acid, two fatty acids that are present in large amounts in fatty livers, decreased significantly in EGCG treated mice. Further tests revealed an increase in hepatic energy stores (one of the liver's functions is to store energy in the form of glycogen) in EGCG mice and showed that EGCG was acting as an antioxidant, thereby protecting fatty livers from I/R injury. In addition, the study showed that EGCG reduced liver fat content by approximately 55 percent. "Significant differences to the fat content, energy stores and markers of cellular injury were observed regardless of how the compound was administered," the authors note.
The authors conclude that "the data presented here indicates that EGCG protects the steatotic liver from I/R injury by reducing hepatic fat content, increasing energy stores, serving as an antioxidant and may stimulate the production of additional antioxidants such as GSH." They add that these activities warrant further investigation and that a thorough understanding of how ECGC acts may suggest its use as a therapeutic agent for fatty livers used in liver transplants.
Article: "Short-Term Administration of (-)-Epigallocatechin Gallate Reduces Hepatic Steatosis and Protects Against Warm Hepatic Ischemia/Reperfusion Injury in Steatotic Mice," Ryan N. Fiorini, Jennifer Donovan, David Rodwell, Zachary Evans, Gang Cheng, Harold May, Charles E. Milliken, John Markowitz, Crystal Campbell, Julia K. Haines, Michael G. Schmidt, Kenneth D. Chavin, Liver Transplantation, 11:3; March 2005 (DOI: 10.1002/lt.20348).