A Green Tea Extract Could Help Alleviate Shortage Of Livers Available For Transplant

Background

Liver transplantation represents the most effective therapy for end-stage liver diseases. However, a severe shortage of donor livers strictly limits the use of this life-saving technique. Consequently, many patients die because they never receive a transplant. For example, about 18,000 patients are currently waiting for donor livers in USA; however, less than 5,000 liver transplantations were performed in 2000. As a result, the number of patients on waiting lists continues to increase. Moreover, shortage of donor livers is exacerbated because some donor organs are unusable, and primary graft failure, which occurs in five to 15 percent of cases, often necessitates retransplantation.

A major source of donor livers is brain-dead accident victims, and accidents are associated overwhelmingly with alcohol. Therefore, alcohol consumption is likely to be a common characteristic of organ donors. Unfortunately, alcohol consumption causes fatty infiltration (deposit of fat within the tissues). Fatty grafts exhibit higher rates of primary graft failure leading to higher death rate; therefore, fatty livers are often not accepted for transplantation.

Previous studies have demonstrated that production of free radicals, an atom or atom group carrying an unpaired electron and no charge, increased in fatty livers after liver transplantation. This increase has been associated with liver graft injury and failure.

Polyphenols are efficient free radical and single oxygen scavengers, and green tea extracts inhibit lipid peroxidation in experimental animals and humans. Green tea contains high levels of polyphenols including catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate and gallocatechin gallate. Considerable epidemiological and experimental evidence shows beneficial effects of green tea extract in reducing the risk of heart disease and cancer, most likely due to the antioxidant property of polyphenols.

Previous studies conducted by North Carolina researchers showed that the feeding of green tea extract dramatically decreased liver injury after warm ischemia/reperfusion, or the return of blood flow, in a rat model, indicating that green tea extract could be an effective therapy clinically to prevent hepatic injury in disease status where an inadequate supply of blood occurs, such as trauma, hemorrhagic shock and hepatic surgery including tumor resection and transplantation.

The Study

Zhi Zhong, PhD., John J. Lemasters, M.D., Ph.D., Ronald G. Thurman, PhD., and their colleagues from the Departments of Cell & Developmental Biology and Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina and Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, NC set out to test the hypothesis that green tea extract blocks free radical formation and thus prevents primary graft failure after transplantation of fatty livers from ethanol-fed rats. Dr. Zhong will present the findings from their study entitled, "Extracts of Polyphenols from Camellia sinenesis (Green Tea) Prevent Primary Graft Failure after Transplantation of Fatty Livers,” during the American Physiological Society (APS) annual meeting, which is being held as part of the Experimental Biology (EB ’02) meeting. More than 12,000 scientific investigators are attending the conference, which begins April 20-24, 2002 at the Ernest N. Morial Convention Center, New Orleans, LA.

Methodology

An inebriating dose of alcohol was given to rats by gavage to mimic binge drinking. Livers were explanted 20 hours later, stored in University of Wisconsin cold storage solution for 24 hours and rinsed with lactated Ringer’s solution containing green tea extract prior to implantation. Free radicals in bile were trapped with a-(4-pyridyl 1-oxide)-N-tert-butylnitrone (4-POBN) and measured using an electron spin resonance spectrometer. 4-Hydroxynenonal, an end-product of lipid peroxidation, was detected immunohistochemically. Transaminase release, liver pathology, and graft survival after transplantation were observed.

Results

· Transaminase or enzyme release after liver transplantation was 4-fold higher in rats that received fatty grafts than in rats with healthy control grafts.

· Ethanol also caused severe focal necrosis in the liver and decreased survival rates from 88 percent to 13 percent.

· Green tea extract largely blunted graft injury and increased survival of fatty livers to 75 percent.

· Ethanol administered to donor rats increased POBN/radical adducts 2.5-fold and caused accumulation of 4-hydroxynenonal, a product of lipid peroxidation, after transplantation. These effects were largely blocked by green tea extract or epigallocatechin gallate, a major polyphenolic component of green tea extract.

Conclusion

The study confirms the association of increased free radical formation and graft failure after transplantation of fatty livers from ethanol-treated donors. Further, the work documents that scavenging of free radicals in fatty livers by green tea extract prevents such liver graft damage and failure. Green tea polyphenols could thus be an effective therapy to prevent failure of fatty grafts after clinical liver transplantation and lead to the inclusion of previously rejected livers into the pool of organs available for transplantation.

The American Physiological Society (APS) is one of the world’s most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions underlying human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.