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Metabonomic Variations Associated with AOM-induced Precancerous Colorectal Lesions and Resveratrol Treatment.
MedLine Citation:
PMID:  22519469     Owner:  NLM     Status:  Publisher    
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 anti-cancer 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 anti-oxidant mechanisms in addition to amelioration of AOM-induced mitochondrial disruption.
Wen Liao; Hai Wei; Xiaoyan Wang; Yunping Qiu; Xiaojun Gou; Xiaolei Zhang; Mingmei Zhou; Jianbing Wu; Tao Wu; Fang Kou; Yongyu Zhang; Zhaoxiang Bian; Guoxiang Xie; Wei Jia
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-20
Journal Detail:
Title:  Journal of proteome research     Volume:  -     ISSN:  1535-3907     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101128775     Medline TA:  J Proteome Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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