4-Vinyl-2,6-dimethoxyphenol (canolol) suppresses oxidative stress and gastric carcinogenesis in Helicobacter pylori-infected carcinogen-treated Mongolian gerbils

Xueyuan Cao, Tetsuya Tsukamoto, Takahiro Seki, Harunari Tanaka, Shigeru Morimura, Liyu Cao, Tsutomu Mizoshita, Hisayo Ban, Takeshi Toyoda, Hiroshi Maeda, Masae Tatematsu

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Oxidative stress is linked to gastric carcinogenesis because of its ability to damage DNA. Here we examined antioxidative and antiinflammatory effects of 4-vinyl-2,6-dimethoxyphenol (canolol), a recently identified potent antioxidative compound obtained from crude canola oil, on Helicobacter (H.) pylori-induced gastritis and gastric carcinogenesis using a Mongolian gerbil model. The animals were allocated to H. pylori-infection alone (12 weeks) or H. pylori + N-methyl-N-nitrosourea (MNU) administration (52 weeks). After oral inoculation of H. pylori, they were fed for 10 and 44 weeks with or without 0.1% canolol. H. pylori-induced gastritis, 5′-bromo-2′-deoxyuridine (BrdU) labeling and scores for cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) immunohistochemistry were attenuated in the canolol-treated groups. Expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), COX-2 and iNOS mRNA in the gastric mucosa, and serum 8-hydroxy-2′-deoxyguanosine (8-OHdG), anti-H. pylori IgG and gastrin levels were also significantly lower in canolol-treated groups. Furthermore, the incidence of gastric adenocarcinomas was markedly reduced in the H. pylori + MNU + canolol-treated group [15.0% (6/40)] compared to the control group [39.4% (13/33)] (p < 0.05). These data indicate canolol to be effective for suppressing inflammation, gastric epithelial cell proliferation and gastric carcinogenesis in H. pylori-infected Mongolian gerbils. Interestingly, the viable H. pylori count was not changed by the canolol containing diet. Thus, the data point to the level of inflammation because of H. pylori rather than the existence of the bacteria as the determining factor. Importantly, canolol appears to suppress induction of mRNAs for inflammatory cytokines.

Original languageEnglish
Pages (from-to)1445-1454
Number of pages10
JournalInternational Journal of Cancer
Volume122
Issue number7
DOIs
Publication statusPublished - 01-04-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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