4-Vinyl-2,6-dimethoxyphenol (canolol) suppresses oxidative stress and gastric carcinogenesis in Helicobacter pylori-infected carcinogen-treated Mongolian gerbils.
Oxidative stress is linked to gastric carcinogenesis because of its ability to damage DNA. Here we examined antioxidative and anti-inflammatory 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-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), 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.
Cao
Xueyuan
X
Division of Oncological Pathology, Aichi Cancer Center Research Institute, Aichi, Japan.
Tsukamoto
Tetsuya
T
Seki
Takahiro
T
Tanaka
Harunari
H
Morimura
Shigeru
S
Cao
Liyu
L
Mizoshita
Tsutomu
T
Ban
Hisayo
H
Toyoda
Takeshi
T
Maeda
Hiroshi
H
Tatematsu
Masae
M
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000907:Antibodies, Bacterial / Q000097:blood; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005755:Gastrins / Q000097:blood; D005756:Gastritis / Q000150:complications* / Q000378:metabolism / Q000382:microbiology; D005849:Gerbillinae; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism; D016480:Helicobacter pylori; D007074:Immunoglobulin G / Q000097:blood; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014753:Vinyl Compounds / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D000907:Antibodies, Bacterial; D000975:Antioxidants; D015415:Biomarkers; D005755:Gastrins; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D010636:Phenols; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014753:Vinyl Compounds; D000080242:8-Hydroxy-2'-Deoxyguanosine; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D003849:Deoxyguanosine; C488411:4-vinyl-2,6-dimethoxyphenol