Zhu B Z, Har-El R, Kitrossky N, Chevion M
Department of Cellular Biochemistry, Hebrew University-Hadassah School of Medicine, Jerusalem, Israel.
Free Radic Biol Med. 1998 Jan 15;24(2):360-9. doi: 10.1016/s0891-5849(97)00220-7.
Desferrioxamine (DFO) is a common drug used in the treatment of iron overload. In addition to its iron-chelation, other properties have been identified. Alas, DFO has demonstrable effects which cannot be explained by its classically established properties; i.e., DFO protects against DNA single strand breaks induced by tetrachlorohydroquinone (TCHQ), while other iron chelators such as DTPA (diethylenetriaminepentaacetic acid) do not. The autooxidation process of TCHQ yielding the tetrachlorosemiquinone radical (TCSQ.) intermediate, was studied here in the presence of chelators. DFO led to a marked reduction in both concentration and life span of TCSQ. via formation of DFO-nitroxide radical (DFO.). In contrast, DTPA had no detectable effect on TCHQ autooxidation. Present studies indicate that the protective effects of DFO on TCHQ-induced DNA damage were not due to the binding of iron, but rather to scavenging of the reactive TCSQ. and the formation of the less reactive DFO.. An additional mode of action of DFO was identified, via stimulation of the hydrolysis (dechlorination) of tetrachloro-1,4-benzoquinone (chloranil), which is the oxidation product of TCHQ, to form 2,5-dichloro-3,6-dihydroxy-1,4-benzoquinone (chloranilic acid). The results of this study demonstrate two new modes of action for DFO: the scavenging of deleterious semiquinone radical, and the stimulation of the hydrolysis of halogenated substituents on the quinone structure. Both modes might prove highly relevant to the biological activities of DFO.
去铁胺（DFO）是治疗铁过载的常用药物。除了其铁螯合作用外，还发现了其他特性。遗憾的是，DFO具有一些无法用其经典确定的特性来解释的明显作用；即，DFO可防止四氯对苯二酚（TCHQ）诱导的DNA单链断裂，而其他铁螯合剂如二乙三胺五乙酸（DTPA）则不能。本文在螯合剂存在的情况下研究了TCHQ产生四氯半醌自由基（TCSQ.）中间体的自氧化过程。DFO通过形成DFO-氮氧化物自由基（DFO.）导致TCSQ的浓度和寿命显著降低。相比之下，DTPA对TCHQ自氧化没有可检测到的影响。目前的研究表明，DFO对TCHQ诱导的DNA损伤的保护作用不是由于铁的结合，而是由于清除反应性TCSQ.并形成反应性较低的DFO.。通过刺激四氯-1,4-苯醌（四氯苯醌）（TCHQ的氧化产物）水解（脱氯）形成2,5-二氯-3,6-二羟基-1,4-苯醌（氯冉酸），确定了DFO的另一种作用方式。本研究结果证明了DFO的两种新作用方式：清除有害的半醌自由基以及刺激醌结构上卤代取代基的水解。这两种作用方式可能都与DFO的生物学活性高度相关。
