Desferrioxamine (Desferal) and superoxide free radicals. Formation of an enzyme-damaging nitroxide

Abstract

In neutral solutions, desferrioxamine (Desferal) can react with the superoxide free radical, O2.- (possibly through its protonated form HO2.), to form a relatively stable nitroxide free radical, which can have a half-life of approx. 10 min at room temperature. The formation of the radical can be largely prevented by the presence of superoxide dismutase. The radical reacts rapidly with cysteine, methionine, glutathione, vitamin C and a water-soluble derivative of vitamin E. It also reacts rapidly with alcohol dehydrogenase, causing a loss of enzyme activity. The implications of these findings for mechanistic free-radical biochemistry and iron-chelation therapy could be considerable.

Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin

“…The main target of free radicals are lipids, nucleic acids, carbohydrates and proteins. As a result of oxidative reactions, proteins undergo proteolysis, structural changes, aberrant aggregation and oxidation of the side chains of amino acids [26,27]. Indeed, modifications of protein molecular weight due to the formation of intramolecular bonds and their cleavage into peptides have been consistently reported [26,27].…”

“…As a result of oxidative reactions, proteins undergo proteolysis, structural changes, aberrant aggregation and oxidation of the side chains of amino acids [26,27]. Indeed, modifications of protein molecular weight due to the formation of intramolecular bonds and their cleavage into peptides have been consistently reported [26,27]. Sulphurcontaining amino acids such as cysteine and methionine are more susceptible to ROS attack [28].…”

Superoxide-dependent consumption of nitric oxide in biological media may confound in vitro experiments

“…A lack of effect of DTPA could be explained by the iron-DTPA complex continuing to catalyse oxygen radical generation [28]. Conversely, the effect of deferoxamine may be explained by the ability of this compound to scavenge free radicals, including O # d − [29], rather than sequester iron. Thus, whereas metal con- taminants are still good candidates, unambiguous evidence for their involvement is difficult to obtain.…”

Effect of Antioxidant Treatment of Streptozotocin-Induced Diabetic Rats on Endoneurial Blood Flow, Motor Nerve Conduction Velocity, and Vascular Reactivity of Epineurial Arterioles of the Sciatic Nerve

“…Laser settings were identical for acquisition of all images from control and diabetic specimens. It has been reported that desferrioxamine at high concentrations in vitro can react with superoxide to form a nitroxide free radical (36,37). To determine whether HES-DFO acutely reacts with superoxide produced by vessels, we preincubated epineurial vessels from a diabetic rat with 1 mmol/l, 100 mol/l, or 10 mol/l HES-DFO or hydroxyethyl starch alone for 30 min.…”