TY - JOUR

T1 - Effective inhibition of copper-catalyzed production of hydroxyl radicals by deferiprone

AU - Timoshnikov, V. A.

AU - Kobzeva, T.

AU - Selyutina, O. Y.

AU - Polyakov, N. E.

AU - Kontoghiorghes, G. J.

PY - 2019/5

Y1 - 2019/5

N2 - Copper ions can catalyze the production of free oxygen radicals (•OH and •OOH) similar to iron ions. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced toxicity in copper-related diseases where there is an increase in copper levels and also when Cu homeostasis and regulation are disrupted. An antioxidant/chelator inhibiting Cu-induced oxidative damage could play a significant role in the treatment of such Cu-related diseases. Deferiprone has high affinity for copper binding and can be considered for the potential treatment of copper toxicity and overloading conditions, such as Wilson’s disease. In the present study, the ability of deferiprone to inhibit the production of hydroxyl radicals catalyzed by copper ions was elucidated using an Electron Paramagnetic Resonance (EPR) spin trapping technique. The values of g-factors and hyperfine splitting constants were calculated for Cu(II)-deferiprone 1:1 complex: (a = 58.5 G, g = 2.1667) and 1:2 complex: (a = 73.0 G, g = 2.1378). The TMIO spin trap (2,2,4-trimethyl-2H-imidazole-1-oxide) was used for the detection of free radicals formed in Fenton-like copper-catalyzed reactions. It was demonstrated that the interaction of deferiprone with Cu 2+ ions completely inhibited hydroxyl radical (•OH) production in the presence of hydrogen peroxide. It was found also that deferiprone inhibits Cu-induced oxidation of linoleic acid in micellar solution. In addition to existing data for water solutions, the affinity of deferiprone for copper binding in non-aqueous environment has been elucidated.

AB - Copper ions can catalyze the production of free oxygen radicals (•OH and •OOH) similar to iron ions. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced toxicity in copper-related diseases where there is an increase in copper levels and also when Cu homeostasis and regulation are disrupted. An antioxidant/chelator inhibiting Cu-induced oxidative damage could play a significant role in the treatment of such Cu-related diseases. Deferiprone has high affinity for copper binding and can be considered for the potential treatment of copper toxicity and overloading conditions, such as Wilson’s disease. In the present study, the ability of deferiprone to inhibit the production of hydroxyl radicals catalyzed by copper ions was elucidated using an Electron Paramagnetic Resonance (EPR) spin trapping technique. The values of g-factors and hyperfine splitting constants were calculated for Cu(II)-deferiprone 1:1 complex: (a = 58.5 G, g = 2.1667) and 1:2 complex: (a = 73.0 G, g = 2.1378). The TMIO spin trap (2,2,4-trimethyl-2H-imidazole-1-oxide) was used for the detection of free radicals formed in Fenton-like copper-catalyzed reactions. It was demonstrated that the interaction of deferiprone with Cu 2+ ions completely inhibited hydroxyl radical (•OH) production in the presence of hydrogen peroxide. It was found also that deferiprone inhibits Cu-induced oxidation of linoleic acid in micellar solution. In addition to existing data for water solutions, the affinity of deferiprone for copper binding in non-aqueous environment has been elucidated.

KW - Copper chelation

KW - Copper toxicity

KW - Deferiprone

KW - EPR

KW - Hydroxyl radical

KW - ENZYME-ACTIVITIES

KW - LIPID-PEROXIDATION

KW - ANTIOXIDANTS

KW - COMPLEXES

KW - CAROTENOIDS

KW - IRON OVERLOAD

KW - DISEASE

KW - HYDROGEN-PEROXIDE

KW - COPPER(II)-INDUCED OXIDATIVE STRESS

UR - http://www.scopus.com/inward/record.url?scp=85062959038&partnerID=8YFLogxK

U2 - 10.1007/s00775-019-01650-9

DO - 10.1007/s00775-019-01650-9

M3 - Article

C2 - 30868263

AN - SCOPUS:85062959038

VL - 24

SP - 331

EP - 341

JO - Journal of Biological Inorganic Chemistry

JF - Journal of Biological Inorganic Chemistry

SN - 0949-8257

IS - 3

ER -