PMID: 9433912Jan 20, 1998Paper

New modes of action of desferrioxamine: scavenging of semiquinone radical and stimulation of hydrolysis of tetrachlorohydroquinone

Free Radical Biology & Medicine
B Z ZhuM Chevion

Abstract

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)....Continue Reading

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