Murakami Keiko, Ishida Kumiko, Watakabe Kyoko, Tsubouchi Ryoko, Haneda Miyako, Yoshino Masataka
Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi 480-1195, Japan.
Biometals. 2006 Jun;19(3):253-7. doi: 10.1007/s10534-005-6998-y.
Maltol (3-hydroxy-2-methyl-4-pyrone) produced reactive oxygen species as a complex with transition metals. Maltol/iron complex inactivated aconitase the most sensitive enzyme to oxidative stress. The inactivation of aconitase was iron-dependent, and prevented by TEMPOL, a scavenger of reactive oxygen species, suggesting that the maltol/iron-mediated generation of superoxide anion is responsible for the inactivation of aconitase. Addition of maltol effectively enhanced the ascorbate/copper-mediated formation of 8-hydroxy-2'-deoxyguanosine in DNA. Oxidation of ascorbic acid by CuSO(4) was effectively stimulated by addition of maltol, and the enhanced oxidation rate was markedly inhibited by the addition of catalase and superoxide dismutase. These results suggest that maltol can stimulate the copper reduction coupled with the oxidation of ascorbate, resulting in the production of superoxide radical which in turn converts to hydrogen peroxide and hydroxyl radical. Cytotoxic effect of maltol can be explained by its prooxidant properties: maltol/transition metal complex generates reactive oxygen species causing the inactivation of aconitase and the production of hydroxyl radical causing the formation of DNA base adduct.
麦芽酚（3-羟基-2-甲基-4-吡喃酮）与过渡金属形成复合物时会产生活性氧。麦芽酚/铁复合物使乌头酸酶失活，乌头酸酶是对氧化应激最敏感的酶。乌头酸酶的失活依赖于铁，并且可被活性氧清除剂TEMPOL阻止，这表明麦芽酚/铁介导的超氧阴离子生成是乌头酸酶失活的原因。添加麦芽酚有效地增强了抗坏血酸/铜介导的DNA中8-羟基-2'-脱氧鸟苷的形成。添加麦芽酚有效地刺激了硫酸铜对抗坏血酸的氧化，并且添加过氧化氢酶和超氧化物歧化酶可显著抑制增强的氧化速率。这些结果表明麦芽酚可以刺激与抗坏血酸氧化偶联的铜还原，从而产生活性氧自由基，进而转化为过氧化氢和羟基自由基。麦芽酚的细胞毒性作用可以用其促氧化特性来解释：麦芽酚/过渡金属复合物产生活性氧，导致乌头酸酶失活，产生的羟基自由基导致DNA碱基加合物的形成。
