Trapping of Phenylacetaldehyde as a Key Mechanism Responsible for Naringenin’s Inhibitory Activity in Mutagenic 2-Amino-1-methyl-6-phenylimidazo [4,5-b]Pyridine Formation

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• 作者：Ka-Wing Cheng ; Chi Chun Wong ; Chi Kong Cho ; Ivan K. Chu ; Kong Hung Sze ; Clive Lo ; Feng Chen ; Mingfu Wang
• 刊名：Chemical Research in Toxicology
• 出版年：2008
• 出版时间：October 20, 2008
• 年：2008
• 卷：21
• 期：10
• 页码：2026-2034
• 全文大小：200K
• 年卷期：v.21,no.10(October 20, 2008)
• ISSN：1520-5010

文摘

Chemical model reactions were carried out to investigate the mechanism of inhibition by a citrus flavonoid, naringenin, on the formation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine found in foods. GC-MS showed that naringenin dose dependently reduced the level of phenylacetaldehyde, a key intermediate on the pathway to the formation of PhIP. Subsequent LC-MS analyses of samples from a wide range of model systems consisting of PhIP precursors, including phenylalanine, glucose, and creatinine, suggested that naringenin scavenged phenylacetaldehyde via adduct formation. An isotope-labeling study showed that the postulated adducts contain fragment(s) of phenylalanine origin. Direct reaction employing phenylacetaldehyde and naringenin further confirmed the capability of naringenin to form adducts with phenylacetaldehyde, thus reducing its availability for PhIP formation. Two of the adducts were subsequently isolated and purified. Their structure was elucidated by one- and two-dimensional NMR spectroscopy as 8-C-(E-phenylethenyl)naringenin (1) and 6-C-(E-phenylethenyl)naringenin (2), respectively, suggesting that C-6 and C-8 are two of the active sites of naringenin in adduct formation. These two adducts were also identified from thermally processed beef models, highlighting phenylacetaldehyde trapping as a key mechanism of naringenin to inhibit PhIP formation.