The iron complex of Dp44mT is redox-active and induces hydroxyl radical formation - an EPR study
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The iron complex of Dp44mT is redox-active and induces hydroxyl radical formation - an EPR study. / Jansson, Patric J; Hawkins, Clare L; Lovejoy, David B; Richardson, Des R.
In: Journal of Inorganic Biochemistry, Vol. 104, No. 11, 11.2010, p. 1224-8.Research output: Contribution to journal › Journal article › peer-review
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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
VL - 104
SP - 1224
EP - 1228
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
SN - 0162-0134
IS - 11
ER -
ID: 174497472