Coordination of iron ions in the form of histidinyl dinitrosyl complexes does not prevent their genotoxicity

Formation of glutathionyl dinitrosyl iron complexes protects against iron genotoxicity

“…5) to have a minor effect on the DNIC concentration. Contrary to the previously studied DNIC containing histidine as an auxiliary ligand, 62 the presently studied DNIC with glutathione was decomposed only to a small extent upon 20 min treatment with DFO (see Fig. 5a-c).…”

“…This might be explained in the light of the previously reported circular dichroism results showing that at pH 7 or above there is no interaction between the DNA strand and the Fe 2+ ions (regardless of the ligand effect). 62 It is noteworthy that we found that in the presence of oxygen the glutathionyl complex hampers radical formation by Fenton type reactions and protects DNA from oxidative damage. Such a protective effect is surely not mediated simply by summarised effects of the DNIC components.…”

“…97 Under normal conditions, pH ca. 7.2, the presence of labile iron does not cause a particular threat to the double helix DNA, as the iron ions do not seem to interact with the DNA helix in the pH above 7 62 (see Fig. 7).…”

“…In order to estimate the stability of the obtained DNICs and relate it to the previously studied histidinyl complex, 62 the preparation was incubated with ten times molar excess of deferoxamine (170 µM DNICs vs. 2 mM DFO) for 20 min at room temperature.…”

“…The herein presented results on the thiolate-type dinitrosylato-iron complex complement a previously published study on the low-molecular-weight dinitrosyl complex of iron with histidines as auxiliary ligands. 62…”