Glutathione-dependent generation of reactive oxygen species by the peroxidase-catalyzed redox cycling of flavonoids

Chem Res Toxicol. 1999 Jun;12(6):521-5. doi: 10.1021/tx980271b.

Abstract

Catalytic concentrations of apigenin (a flavone containing a phenol B ring) and naringin or naringenin (flavanones containing a phenol B ring) caused extensive GSH oxidation at a physiological pH in the presence of peroxidase. Only catalytic H2O2 concentrations were required, indicating a redox cycling mechanism that generated H2O2 was involved. Extensive oxygen uptake ensued, the extent of which was proportional to the extent of GSH oxidation to GSSG and was markedly increased by superoxide dismutase. These results suggest that prooxidant phenoxyl radicals formed by these flavonoids co-oxidized GSH to form thiyl radicals which activated oxygen. GSH also prevented the peroxidase-catalyzed oxidative destruction of these flavonoids which suggests that phenoxyl radicals initiated the oxidative destruction. This is the first time that a group of flavonoids have been identified as prooxidants independent of autoxidation reactions catalyzed by the transition metal ions Fe3+, Fe2+, Mn2+, and Cu2+.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Flavonoids / metabolism*
  • Free Radicals
  • Glutathione / metabolism*
  • Oxidation-Reduction
  • Peroxidases / metabolism*
  • Phenols / metabolism
  • Reactive Oxygen Species / metabolism*

Substances

  • Flavonoids
  • Free Radicals
  • Phenols
  • Reactive Oxygen Species
  • phenoxy radical
  • Peroxidases
  • Glutathione