Peroxidative metabolism of apigenin and naringenin versus luteolin and quercetin: glutathione oxidation and conjugation.
GSH was readily depleted by a flavonoid, H(2)O(2), and peroxidase mixture but the products formed were dependent on the redox potential of the flavonoid. Catalytic amounts of apigenin and naringenin but not kaempferol (flavonoids that contain a phenol B ring) when oxidized by H(2)O(2) and peroxidase co-oxidized GSH to GSSG via a thiyl radical which could be trapped by 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) to form a DMPO-glutathionyl radical adduct detected by ESR spectroscopy. On the other hand, quercetin and luteolin (flavonoids that contain a catechol B ring) or kaempferol depleted GSH stoichiometrically without forming a thiyl radical or GSSG. Quercetin, luteolin, and kaempferol formed mono-GSH and bis-GSH conjugates, whereas apigenin and naringenin did not form GSH conjugates. MS/MS electrospray spectroscopy showed that mono-GSH conjugates for quercetin and luteolin had peaks at m/z 608 [M + H](+) and m/z 592 [M + H](+) in the positive-ion mode, respectively. (1)H NMR spectroscopy showed that the GSH was bound to the quercetin A ring. Spectral studies indicated that at a physiological pH the luteolin-SG conjugate was formed from a product with a UV maximum absorbance at 260 nm that was reducible by potassium borohydride. The quercetin-SG conjugate or kaempferol-SG conjugate on the other hand was formed from a product with a UV maximum absorbance at 335 nm that was not reducible by potassium borohydride. These results suggest that GSH was oxidized by apigenin/naringenin phenoxyl radicals, whereas GSH conjugate formation involved the o-quinone metabolite of luteolin or the quinoid (quinone methide) product of quercetin/kaempferol.
Galati
G
G
Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
Moridani
M Y
MY
Chan
T S
TS
O'Brien
P J
PJ
D047310:Apigenin; D002374:Catalase / Q000378:metabolism; D004578:Electron Spin Resonance Spectroscopy; D044950:Flavanones; D005419:Flavonoids / Q000378:metabolism*; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D047311:Luteolin; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D011794:Quercetin / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D044950:Flavanones; D005419:Flavonoids; D005609:Free Radicals; D047310:Apigenin; D011794:Quercetin; D006861:Hydrogen Peroxide; D006735:Horseradish Peroxidase; D002374:Catalase; D005978:Glutathione; C005273:naringenin; D047311:Luteolin