Document Type

Journal Article

Authors

Wen Liao, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Hai Wei, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Xiaoyan Wang, Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University
Yunping Qiu, Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus
Xiaojun Gou, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Xiaolei Zhang, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Mingmei Zhou, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Jianbing Wu, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Tao Wu, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Fang Kou, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Yongyu Zhang, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine
Zhaoxiang Bian, School of Chinese Medicine, Hong Kong Baptist Universit
Guoxiang Xie, Department of Nutrition, University of North Carolina at Greensboro, North Carolina Research Campus
Wei Jia, Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine

Department/Unit

School of Chinese Medicine

Title

Metabonomic variations associated with AOM-induced precancerous colorectal lesions and resveratrol treatment

Language

English

Abstract

Resveratrol (Res), 3,5,4′-trihydroxy-trans-stilbene, is an antioxidant found in the skin of red grapes and in several other plants. This phenolic compound has been recently reported to possess cancer chemopreventive activity that inhibits the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the chemoprotective effects of dietary Res in an azoxymethane (AOM) induced precancerous colorectal lesion model in male Wistar rats. The metabolic alterations in urine, sera, and colonic tissues of experimental rats perturbed by AOM intervention as well as the Res treatment were measured by a gas chromatography time-of-flight mass spectrometry (GC-TOFMS) analysis. Significant alterations of metabolites were observed in AOM group in urine, sera, and colonic tissues, which were attenuated by Res treatment and concurrent with the histopathological improvement with significantly decreased aberrant crypt foci (ACF) incidence. Representative metabolites include depleted glucose, β-hydroxybutyrate (ketone body), hypoxanthine, and elevated branched chain amino acids (isoleucine and valine) and tryptophan in colonic tissue, as well as elevated serum aminooxyacetate and urinary 4-hydroxyphenylacetate and xanthurenate. These metabolic changes suggest that the preventive effect of Res is associated with attenuation of impaired glucose and lipid metabolism and elevated protein breakdown in colonic tissues from AOM-exposed rats. It also appears that Res induced significant metabolic alterations independent of the AOM-induced metabolic changes. The significantly altered metabolites identified in Res-AOM group relative to AOM group include arachidonate, linoleate, glutamate, docosahexaenoate, palmitelaidate, 2-aminobutyrate, pyroglutamate, and threonate, all of which are involved in inflammation and oxidation processes. This suggests that Res exerts the chemopreventive effects on ACF formation by anti-inflammatory and antioxidant mechanisms in addition to amelioration of AOM-induced mitochondrial disruption. © 2012 American Chemical Society.

Keywords

AOM, azoxymethane, colorectal cancer, gas chromatography time-of-flight mass spectrometry, GC-TOFMS, metabonomics, resveratrol

Publication Date

2012

Source Publication Title

Journal of Proteome Research

Volume

11

Issue

6

Start Page

3436

End Page

3448

Publisher

American Chemical Society

DOI

10.1021/pr300284h

Link to Publisher's Edition

http://dx.doi.org/10.1021/pr300284h

ISSN (print)

15353893

ISSN (electronic)

15353907

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