An essential difference in the reactivity of the glutathione adducts of the structurally closely related flavonoids monoher and quercetin

H. Jacobs*, M. Moalin, M.W. van Gisbergen, A. Bast, W.J.F. van der Vijgh, G.R.M.M. Haenen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

During the scavenging of free radicals flavonoids are oxidized to electrophilic quinones. Glutathione (GSH) can trap these quinones, thereby forming GSH-flavonoid adducts. The aim of this study was to compare the stability of the GSH-flavonoid adduct of 7-mono-O-(beta-hydroxyethyl)rutoside (monoHER) with that of quercetin. It was found that GSH-quercetin reacts with the thiol N-acetyl-l-cysteine (NAC) to form NAC-quercetin, whereas GSH-monoHER does not react with NAC. In addition, the adduct of the monoHER quinone with the dithiol dithiothreitol (DTT) is relatively stable, whereas the DTT-quercetin adduct is readily converted into quercetin and DTT disulfide. These differences in reactivity of the thiol-flavonoid adducts demonstrate that GSH-monoHER is much more stable than GSH-quercetin. This difference in reactivity was corroborated by molecular quantum chemical calculations. Thus, although both flavonoid quinones are rapidly scavenged by GSH, the advantage of monoHER is that it forms a stable conjugate with GSH, thereby preventing a possible spread of toxicity. These findings demonstrate that even structurally comparable flavonoids behave differently, which will be reflected in the biological effects of these flavonoids.
Original languageEnglish
Pages (from-to)2118-2123
Number of pages6
JournalFree Radical Biology and Medicine
Volume51
Issue number11
DOIs
Publication statusPublished - 1 Dec 2011

Keywords

  • 7-Mono-O-(beta-hydroxyethyl)rutoside
  • MonoHER
  • Flavonoid
  • Antioxidant
  • Quercetin
  • Glutathione
  • Thiols
  • Free radicals
  • DOXORUBICIN-INDUCED CARDIOTOXICITY
  • MONOHYDROXYETHYLRUTOSIDE
  • RADICALS
  • ANTIOXIDANT
  • SEMIQUINONE
  • PROOXIDANT
  • OXIDATION
  • TOXICITY
  • THIOLS
  • DAMAGE

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