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Advanced glycation end products (AGE) induce the receptor for AGE in the colonic mucosa of azoxymethane-injected Fischer 344 rats fed with a high-linoleic acid and high-glucose diet

Authors
  • Shimomoto, Takasumi1
  • Luo, Yi1
  • Ohmori, Hitoshi1
  • Chihara, Yoshitomo1
  • Fujii, Kiyomu1
  • Sasahira, Tomonori1
  • Denda, Ayumi1
  • Kuniyasu, Hiroki1
  • 1 Nara Medical University, Department of Molecular Pathology, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan , Kashihara (Japan)
Type
Published Article
Journal
Journal of Gastroenterology
Publisher
Springer Japan
Publication Date
Mar 31, 2012
Volume
47
Issue
10
Pages
1073–1083
Identifiers
DOI: 10.1007/s00535-012-0572-5
Source
Springer Nature
Keywords
License
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Abstract

BackgroundAdvanced glycation end products (AGE) and the receptor for advanced glycation end products (RAGE) are closely associated with colorectal cancer progression. The association between RAGE and AGE in colon carcinogenesis needs to be clarified.MethodsLevels of RAGE and AGE were examined in azoxymethane (AOM)-injected Fischer 344 rats fed a control diet (Group C), a 15 % linoleic acid (LA) diet (Group L), a control diet with 10 % glucose drink (Group G), and a 15 % LA diet with 10 % glucose drink (Group L + G). Group L + G showed the most pronounced increase of body weight, blood sugar, and serum insulin.ResultsThe rats in Group L + G showed the most pronounced multiplicity of aberrant crypt foci (ACF) and carcinomas with increased mucosal RAGE and AGE. IEC6 rat intestinal epithelial cells treated with AGE showed increased RAGE expression, which was inhibited by treatment with metformin or losartan. In the AOM-injected rat colon cancer model, the levels of RAGE and AGE, and the multiplicity of ACF and carcinomas, in Group L + G rats were suppressed by treatment with metformin or losartan.ConclusionsThese results suggest that AGE–RAGE induced by high-LA and high-glucose diets substantially enhances colon cancer development; thus, suppression of AGE–RAGE could be a potential target for colon cancer chemoprevention.

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