The iron complex of Dp44mT is redox-active and induces hydroxyl radical formation - an EPR study

TY - JOUR

T1 - The iron complex of Dp44mT is redox-active and induces hydroxyl radical formation - an EPR study

AU - Jansson, Patric J

AU - Hawkins, Clare L

AU - Lovejoy, David B

AU - Richardson, Des R

N1 - Copyright © 2010. Published by Elsevier Inc.

PY - 2010/11

Y1 - 2010/11

N2 - Iron chelation therapy was initially designed to alleviate the toxic effects of excess iron evident in iron-overload diseases. However, some iron chelator-metal complexes have also gained interest due to their high redox activity and toxicological properties that have potential for cancer chemotherapy. This communication addresses the conflicting results published recently on the ability of the iron chelator, Dp44mT, to induce hydroxyl radical formation upon complexation with iron (B.B. Hasinoff and D. Patel, J Inorg. Biochem.103 (2009), 1093-1101). This previous study used EPR spin-trapping to show that Dp44mT-iron complexes were not able to generate hydroxyl radicals. Here, we demonstrate the opposite by using the same technique under very similar conditions to show the Dp44mT-iron complex is indeed redox-active and induces hydroxyl radical formation. This was studied directly in an iron(II)/H(2)O(2) reaction system or using a reducing iron(III)/ascorbate system implementing several different buffers at pH 7.4. The demonstration by EPR that the Dp44mT-iron complex is redox-active confirms our previous studies using cyclic voltammetry, ascorbate oxidation, benzoate hydroxylation and a plasmid DNA strand-break assay. We discuss the relevance of the redox activity to the biological effects of Dp44mT.

AB - Iron chelation therapy was initially designed to alleviate the toxic effects of excess iron evident in iron-overload diseases. However, some iron chelator-metal complexes have also gained interest due to their high redox activity and toxicological properties that have potential for cancer chemotherapy. This communication addresses the conflicting results published recently on the ability of the iron chelator, Dp44mT, to induce hydroxyl radical formation upon complexation with iron (B.B. Hasinoff and D. Patel, J Inorg. Biochem.103 (2009), 1093-1101). This previous study used EPR spin-trapping to show that Dp44mT-iron complexes were not able to generate hydroxyl radicals. Here, we demonstrate the opposite by using the same technique under very similar conditions to show the Dp44mT-iron complex is indeed redox-active and induces hydroxyl radical formation. This was studied directly in an iron(II)/H(2)O(2) reaction system or using a reducing iron(III)/ascorbate system implementing several different buffers at pH 7.4. The demonstration by EPR that the Dp44mT-iron complex is redox-active confirms our previous studies using cyclic voltammetry, ascorbate oxidation, benzoate hydroxylation and a plasmid DNA strand-break assay. We discuss the relevance of the redox activity to the biological effects of Dp44mT.

KW - Ascorbic Acid

KW - Buffers

KW - DNA Damage

KW - Electron Spin Resonance Spectroscopy

KW - Hydrogen-Ion Concentration

KW - Hydroxyl Radical

KW - Iron

KW - Iron Chelating Agents

KW - Iron Overload

KW - Iron, Dietary

KW - Oxidation-Reduction

KW - Thiosemicarbazones

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.jinorgbio.2010.07.012

DO - 10.1016/j.jinorgbio.2010.07.012

M3 - Journal article

C2 - 20719391

SN - 0162-0134

VL - 104

SP - 1224

EP - 1228

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

IS - 11

ER -