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LIVER AND BILIARY TRACT

Polyphenols from Camellia sinenesis attenuate experimental cholestasis-induced liver fibrosis in rats

Zhi Zhong,¹ Matthias Froh,² Mark Lehnert,¹ Robert Schoonhoven,³ Liu Yang,¹ Henrik Lind,¹ John J. Lemasters,¹ and Ronald G. Thurman^2,

Departments of ¹Cell and Developmental Biology, ²Pharmacology, and ³Environmental Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7090

Submitted 7 January 2003 ; accepted in final form 22 May 2003

Accumulation of hydrophobic bile acids during cholestasis leads to generation of oxygen free radicals in the liver. Accordingly, this study investigated whether 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 before bile duct ligation. After bile duct ligation, serum alanine transaminase increased to 760 U/l after 1 day in rats fed a control diet. Focal necrosis and bile duct proliferation were also observed after 1–2 days, and fibrosis developed 2–3 wk after bile duct ligation. Additionally, procollagen-1(I) mRNA increased 30-fold 3 wk after bile duct ligation, accompanied by increased expression of -smooth muscle actin and transforming growth factor- and the accumulation of 4-hydroxynenonal, an end product of lipid peroxidation. Polyphenol feeding blocked or blunted all of these bile duct ligation-dependent changes by 45–73%. 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.

bile duct ligation; fibrosis; oxidative stress; transforming growth factor-

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