Vol. 283, Issue 4, G957-G964, October 2002
Prevention of hepatic ischemia-reperfusion injury by
green tea extract
Zhi
Zhong1,2,
Matthias
Froh2,
Henry D.
Connor2,
Xiangli
Li2,
Lars
O.
Conzelmann2,
Ronald P.
Mason3,
John J.
Lemasters1, and
Ronald G.
Thurman2,
Departments of 1 Cell and Developmental Biology
and 2 Pharmacology, University of North
Carolina at Chapel Hill 27599; and 3 Laboratory Of
Pharmacology and Chemistry, National Institute of Environmental Health
Sciences, Research Triangle Park, North Carolina 27709
These experiments were designed to determine
whether green tea extract (GTE), which contains polyphenolic free
radical scavengers, prevents ischemia-reperfusion injury to the
liver. Rats were fed a powdered diet containing 0-0.3% GTE
starting 5 days before hepatic warm ischemia and reperfusion.
Free radicals in bile were trapped with the spin-trapping reagent
-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) and measured using electron spin resonance spectroscopy. Hepatic ischemia-reperfusion increased transaminase
release and caused pathological changes including focal necrosis and
hepatic leukocyte infiltration in the liver. Transaminase release was diminished by over 85% and pathological changes were almost totally blocked by 0.1% dietary GTE. Ischemia-reperfusion increased
4-POBN/radical adducts in bile nearly twofold, an effect largely
blocked by GTE. Epicatechin, one of the major green tea polyphenols,
gave similar protection as GTE. In addition, hepatic
ischemia-reperfusion activated NF-
B and increased TNF-
mRNA and protein expression. These effects were all blocked by GTE.
Taken together, these results demonstrate that GTE scavenges free
radicals in the liver after ischemiareoxygenation, thus
preventing formation of toxic cytokines. Therefore, GTE could prove to
be effective in decreasing hepatic injury in disease states where
ischemia-reperfusion occurs.
ischemia; free radicals; liver; nuclear factor-kappaB; cytokines
Deceased 14 July 2001.