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Biometals. 2006 Aug;19(4):429-35.

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.

Author information

1
Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan.

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.

PMID:
16841252
DOI:
10.1007/s10534-005-4528-6
[Indexed for MEDLINE]

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