Generation of reactive oxygen species by hydroxyketone compounds

Summary Deferiprone (3‑hydroxy‑12‑dimethyl‑4‑pyridone a hydroxyketone compound with pyridine ring is a water soluble orally active iron chelator used for the therapy of Friedreichs ataxia and ‑thalassemia. Toxic eff ect of deferiprone was analyzed in relation to the generation of reactive oxygen species. 1. Deferiprone/iron complex inactivated aconitase the most sensitive enzyme to oxidative stress. The inactivation was dependent on sodium azide an inhibitor of cata‑ lase indicating that deferiprone/iron complex can generate hydrogen peroxide as a principal product. Deferiprone was more eff ective on aconitase than maltol or kojic acid hydroxyketone compounds with pyrane ring. 2. Deferiprone maltol and kojic acid stimulated the atuooxidation of Fe 2+ suggesting that these compounds promote the activation of dioxygen molecule by reduced iron. When chelating agents are used for iron storage disease attention should be paid to the transition metal‑complex mediated generation of reactive oxygen species.