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.
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† This paper is dedicated to centennial of the birthday of the late Professor Emeritus Yahito Kotake, a pioneer of the xanthurenic acid research.
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Murakami, K., Haneda, M. & Yoshino, M. 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 19, 429–435 (2006). https://doi.org/10.1007/s10534-005-4528-6
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DOI: https://doi.org/10.1007/s10534-005-4528-6