title: Metabonomic variations associated with AOM-induced precancerous colorectal lesions and resveratrol treatment.
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.
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine , Shanghai 201204, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liao
authors.forename: Hai
authors.initials: H
authors.lastname: Wei
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Gou
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Zhang
authors.forename: Mingmei
authors.initials: M
authors.lastname: Zhou
authors.forename: Jianbing
authors.initials: J
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Kou
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Bian
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Xie
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001397:Azoxymethane; D015179:Colorectal Neoplasms / Q000097:blood* / Q000139:chemically induced / Q000517:prevention & control / Q000652:urine; D008297:Male; D055442:Metabolome; D011230:Precancerous Conditions / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016588:Anticarcinogenic Agents; D013267:Stilbenes; D001397:Azoxymethane; D000077185:Resveratrol