Department of Biochemistry, School of Medicine, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan.
Biometals. 2022 Apr;35(2):329-334. doi: 10.1007/s10534-022-00367-8. Epub 2022 Feb 14.
Prooxidant properties of aminophenol, the constituent of acetaminophen and mesalamine, were examined. Aminophenol compounds/copper-dependent formation of reactive oxygen species was analyzed by the inactivation of aconitase, the most sensitive enzyme to oxidative stress in permeabilized yeast cells. Aminophenol compounds of 2 (ortho)- and 4 (para)- substituents, but not 3 (meta)-isomer produced reactive oxygen species in the presence of copper (cupric) ion or iron. The inactivation required sodium azide the inhibitor of catalase, suggesting that the superoxide radical produced from the 2- and 4-aminophenol in the presence of copper is responsible for the inactivation of aconitase. Aminophenols of 2- and 4-substituents showed a potent reducing activity of copper (cupric) ion, and further potent reactivity with DPPH radical, but 3-aminophenol showed only a little reactivity. Reduced copper ion can generate superoxide radical with the production of oxidized metal. Aminophenols can reduce the copper ion, and further stimulate the continuous production of reactive oxygen species. Cytotoxic effect of acetaminophen, the N-acetylated-p-aminophenol and mesalamine, the 4-aminophenol derivatives may be accounted for by the prooxidant properties of their constituents, aminophenol.
研究了氨基酚（对乙酰氨基酚和柳氮磺胺吡啶的组成部分）的促氧化剂特性。通过测定在通透酵母细胞中对氧化应激最敏感的酶——乌头酸酶的失活情况，分析了氨基酚化合物/铜依赖性活性氧的形成。具有 2（邻位）和 4（对位）取代基的氨基酚化合物，但没有 3（间位）异构体，在铜（铜）离子或铁存在的情况下产生活性氧。失活需要叠氮化钠（过氧化氢酶抑制剂），这表明 2-和 4-氨基酚在铜存在下产生的超氧自由基是导致乌头酸酶失活的原因。2-和 4-取代基的氨基酚具有很强的还原铜（铜）离子的活性，并且与 DPPH 自由基进一步具有很强的反应活性，但 3-氨基酚仅显示出一点反应活性。还原后的铜离子可以与氧化金属一起产生超氧自由基。氨基酚可以还原铜离子，并进一步刺激活性氧的持续产生。对乙酰氨基酚、N-乙酰基-对氨基酚和柳氮磺胺吡啶（4-氨基酚衍生物）的细胞毒性作用可能与其组成部分氨基酚的促氧化剂特性有关。
