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American Journal of Clinical Nutrition, Vol. 80, No. 3, 742-751, September 2004
© 2004 American Society for Clinical Nutrition


ORIGINAL RESEARCH COMMUNICATION

Green tea polyphenols prevent toxin-induced hepatotoxicity in mice by down-regulating inducible nitric oxide–derived prooxidants1,2,3

Ju-Hua Chen, George L Tipoe, Emily C Liong, Henry SH So, Ka-Man Leung, Wai-Ming Tom, Peter CW Fung and Amin A Nanji

1 From the Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland (J-HC); the Departments of Anatomy (GLT and K-ML), Pathology (ECL and HSHS), Pharmacology (W-MT), and Medicine (PCWF) and the Centre for the Study of Liver Disease (GLT and PCWF), Faculty of Medicine, The University of Hong Kong; and the Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia (AAN)

Background: Recently, considerable attention has been focused on dietary and medicinal phytochemicals that inhibit, reverse, or retard diseases caused by oxidative and inflammatory processes. Green tea polyphenols have both antioxidant and antiinflammatory properties.

Objective: We examined the effects of green tea polyphenols in carbon tetrachloride–treated mice, a model of liver injury in which oxidant stress and cytokine production are intimately linked. We tested the effect of a pure form of epigallocatechin gallate (EGCG), the major polyphenol in green tea, in mice treated with carbon tetrachloride.

Design: Eight-week-old ICR mice were administered 20 µL/CCl4 kg dissolved in olive oil. Two different doses of EGCG, 50 and 75 mg/kg, were tested. Control mice were treated with saline and olive oil. We analyzed liver histopathology, lipid peroxidation, and messenger RNA and protein concentrations of inducible nitric oxide synthase. Additionally, nitric oxide–generated radicals were assessed by electron paramagnetic resonance spectroscopy, and protein concentrations were measured by immunohistochemistry and Western blot analysis.

Results: Carbon tetrachloride administration caused an intense degree of liver necrosis associated with increases in lipid peroxidation, inducible nitric oxide synthase messenger RNA and protein, nitrotyrosine, and nitric oxide radicals. EGCG administration led to a dose-dependent decrease in all of the histologic and biochemical variables of liver injury observed in the carbon tetrachloride–treated mice.

Conclusions: Green tea polyphenols reduce the severity of liver injury in association with lower concentrations of lipid peroxidation and proinflammatory nitric oxide–generated mediators. Green tea polyphenols can be a useful supplement in the treatment of liver disease and should be considered for liver conditions in which proinflammatory and oxidant stress responses are dominant.

Key Words: Polyphenols • green tea • nitric oxide • free radicals • lipid peroxidation • carbon tetrachloride




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