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Am J Physiol Gastrointest Liver Physiol (June 4, 2003). doi:10.1152/ajpgi.00008.2003
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Submitted on January 7, 2003
Accepted on May 22, 2003

Polyphenols from Camellia sinensis Attenuate Experimental Cholestasis-Induced Liver Fibrosis in Rats

Zhi Zhong1*, Matthias Froh2, Mark Lehnert1, Robert Schoonhoven3, Liu Yang1, Henrik Lind1, John J. Lemasters1, and Ronald G. Thurman2

1 Department of Cell and Developmental Biology, University of North Carolina, Chapel Hill, NC, USA
2 Department of Pharmacology, University of North Carolina, Chapel Hill, NC, USA
3 Department of Environmental Sciences, University of North Carolina, Chapel Hill, NC, USA

* To whom correspondence should be addressed. E-mail: zzhong{at}med.unc.edu.

Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated if polyphenols from green tea Camellia sinenesis, which are potent free radical scavengers, decrease hepatic injury caused by experimental cholestasis. Rats were fed a standard chow or a diet containing 0.1% polyphenolic extracts from C. sinenesis starting 3 days prior to bile duct ligation. After bile duct ligation, serum alanine transaminase (ALT) increased to 760 U/L after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1 to 2 days, and fibrosis developed 2 to 3 weeks after bile duct ligation. Additionally, procollagen-{alpha}1(I) mRNA increased 30-fold 3 weeks after bile duct ligation, accompanied by increased protein expression of {alpha}-smooth muscle actin and transforming growth factor-{beta} and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all these bile duct ligation-dependent changes by 45 to 73%. Taken together, the results indicate that cholestasis due to bile duct ligation causes liver injury by mechanisms involving oxidative stress. Polyphenols from C. sinenesis scavenge oxygen radicals and prevent activation of stellate cells thereby minimizing liver fibrosis.




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