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Dietary lycopene and tomato extract supplementations inhibit nonalcoholic steatohepatitis‐promoted hepatocarcinogenesis in rats
Author(s) -
Wang Yan,
Ausman Lynne M.,
Greenberg Andrew S.,
Russell Robert M.,
Wang XiangDong
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24689
Subject(s) - proinflammatory cytokine , endocrinology , medicine , lycopene , oxidative stress , glutathione , lipid peroxidation , heme oxygenase , antioxidant , chemistry , biology , biochemistry , inflammation , heme , enzyme
Epidemiological and experimental studies provide supportive evidence that lycopene (LY), a major carotenoid from tomatoes and tomato products, may act as a chemopreventive agent against certain types of cancers. We recently showed that high‐fat diet (HFD)‐induced nonalcoholic steatohepatitis (NASH) promoted diethylnitrosamine (DEN)‐initiated hepatocarcinogenesis in a rat model. Using this model, we investigated the efficacy of an equivalent dosage of dietary LY from either a pure compound or a tomato extract (TE) against NASH‐promoted hepatocarcinogenesis. Six groups of rats were injected with DEN and then fed either Lieber‐DeCarli control diet or HFD with or without LY or TE for 6 weeks. Results showed that both LY and TE supplementations significantly decreased the number of altered hepatic foci expressing the placental form of glutathione S‐transferase in the livers of HFD‐fed rats. This was associated with significantly lower proliferating cell nuclear antigen positive hepatocytes and cyclinD1 protein, as well as decreased activation of extracellular signal‐regulated kinase and nuclear NF‐κB. Although both LY and TE supplementations reduced HFD‐induced lipid peroxidation in the livers, we observed significantly decreased cytochrome P450 2E1, inflammatory foci and mRNA expression of proinflammatory cytokines (TNF‐α, IL‐1β and IL‐12) in the HFD+TE fed group but increased nuclear NF‐E2‐related factor‐2 and heme oxygenase‐1 proteins in the HFD+LY fed group, relative to HFD feeding alone. These data indicate that LY and TE can inhibit NASH‐promoted hepatocarcinogenesis mainly as a result of reduced oxidative stress, which could be fulfilled through different mechanisms.