Prooxidant action of xanthurenic acid and quinoline compounds: role of transition metals in the generation of reactive oxygen species and enhanced formation of 8-hydroxy-2'-deoxyguanosine in DNA

Biometals. 2006 Aug;19(4):429-35. doi: 10.1007/s10534-005-4528-6.

Abstract

Xanthurenic acid, a product of tryptophan-NAD pathway, and quinoline compounds produced reactive oxygen species as a complex with iron. Aconitase, the most sensitive enzyme to oxidative stress was inactivated effectively by xanthurenic acid and to a lesser extent by 8-quinolinol in the presence of ferrous sulfate. The inactivation of aconitase was iron-dependent, and was prevented by TEMPOL, a scavenger of reactive oxygen species, suggesting that reduced iron bound to xanthurenic acid or 8-quinolinol can activate oxygen molecule to form superoxide radical. However, kynurenic acid and quinaldic acid without 8-hydroxyl group did not produce reactive oxygen species. Of the quinoline compounds tested, xanthurenic acid and 8-quinolinol with 8-hydroxyl group stimulated the autooxidation of ferrous ion, but kynurenic acid and quinaldic acid did not affect the oxidation of ferrous ion. Hydroxyl group at 8-positions of quinoline compounds was essential for the binding of iron causing the generation of reactive oxygen species. 8-Quinolinol effectively enhanced the ascorbate/copper-mediated formation of 8-hydroxy-2'-deoxyguanosine in DNA, suggesting the quinolinol/copper-dependent stimulation hydroxyl radical formation. Xanthurenic acid and 8-quinolinol as the metal-chelate complexes can show various cytotoxic effects by generating reactive oxygen species through the ferrous or cuprous ion-dependent activation of oxygen molecule.

MeSH terms

  • Aconitate Hydratase / metabolism
  • DNA / chemistry
  • DNA / metabolism*
  • Dose-Response Relationship, Drug
  • Ferrous Compounds / metabolism
  • Metals / metabolism*
  • Molecular Structure
  • Oxidation-Reduction / drug effects
  • Phosphoric Monoester Hydrolases / metabolism
  • Quinolines / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / metabolism
  • Xanthurenates / pharmacology*

Substances

  • Ferrous Compounds
  • Metals
  • Quinolines
  • Reactive Oxygen Species
  • Xanthurenates
  • xanthurenic acid
  • DNA
  • quinoline
  • glyceraldehyde 3-phosphate phosphatase
  • Phosphoric Monoester Hydrolases
  • Aconitate Hydratase