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.
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.
Cheng
Ka-Wing
KW
School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong 123456, People's Republic of China.
Wong
Chi Chun
CC
Cho
Chi Kong
CK
Chu
Ivan K
IK
Sze
Kong Hung
KH
Lo
Clive
C
Chen
Feng
F
Wang
Mingfu
M
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D000818:Animals; D002417:Cattle; D044950:Flavanones / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism; D013058:Mass Spectrometry; D008460:Meat; D008954:Models, Biological; D015394:Molecular Structure; D016296:Mutagenesis / Q000187:drug effects*
D044950:Flavanones; D007093:Imidazoles; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D000079:Acetaldehyde; C005273:naringenin; C013192:phenylacetaldehyde