Green tea polyphenols prevent toxin-induced hepatotoxicity in mice by down-regulating inducible nitric oxide-derived prooxidants.
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.


METHODS
Eight-week-old ICR mice were administered 20 microL/CCl(4) 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.
Chen
Ju-Hua
JH
Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, USA.
Tipoe
George L
GL
Liong
Emily C
EC
So
Henry S H
HS
Leung
Ka-Man
KM
Tom
Wai-Ming
WM
Fung
Peter C W
PC
Nanji
Amin A
AA
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D012720:Severity of Illness Index; D013662:Tea / Q000737:chemistry*
D000975:Antioxidants; D012333:RNA, Messenger; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D002251:Carbon Tetrachloride; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse