Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts.

A major portion of the toxicity of hydrogen peroxide in Escherichia coli is attributed to DNA damage mediated by a Fenton reaction that generates active forms of hydroxyl radicals from hydrogen peroxide, DNA-bound iron, and a constant source of reducing equivalents. Kinetic peculiarities of DNA damage production by hydrogen peroxide in vivo can be reproduced by including DNA in an in vitro Fenton reaction system in which iron catalyzes the univalent reduction of hydrogen peroxide by the reduced form of nicotinamide adenine dinucleotide (NADH). To minimize the toxicity of oxygen radicals, the cell utilizes scavengers of these radicals and DNA repair enzymes. On the basis of observations with the model system, it is proposed that the cell may also decrease such toxicity by diminishing available NAD(P)H and by utilizing oxygen itself to scavenge active free radicals into superoxide, which is then destroyed by superoxide dismutase.

https://science.sciencemag.org/content/sci/240/4857/1302.full.pdf

DNA damage and oxygen radical toxicity

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2891%2980347-6

DNA damage by oxygen-derived species Its mechanism and measurement in mammalian systems

Superparamagnetic iron oxide nanoparticles (SPION) are being widely used for various biomedical applications, for example, magnetic resonance imaging, targeted delivery of drugs or genes, and in hyperthermia. Although, the potential benefits of SPION are considerable, there is a distinct need to identify any potential cellular damage associated with these nanoparticles. Besides focussing on cytotoxicity, the most commonly used determinant of toxicity as a result of exposure to SPION, this review also mentions the importance of studying the subtle cellular alterations in the form of DNA damage and oxidative stress. We review current studies and discuss how SPION, with or without different surface coating, may cause cellular perturbations including modulation of actin cytoskeleton, alteration in gene expression profiles, disturbance in iron homeostasis and altered cellular responses such as activation of signalling pathways and impairment of cell cycle regulation. The importance of protein-SPION interaction and various safety considerations relating to SPION exposure are also addressed. Keywords: SPION; cellular stress; cytotoxicity; DNA damage (Published: 21 September 2010) Citation: Nano Reviews 2010, 1: 5358 - DOI: 10.3402/nano.v1i0.5358

https://www.tandfonline.com/doi/pdf/10.3402/nano.v1i0.5358

Potential toxicity of superparamagnetic iron oxide nanoparticles (SPION)

Molecular and cellular aspects of thiol-disulfide exchange.

Ferric iron and superoxide ions are required for the killing of cultured hepatocytes by hydrogen peroxide. Evidence for the participation of hydroxyl radicals formed by an iron-catalyzed Haber-Weiss reaction.

P E Starke

Papers

Ferric iron and superoxide ions are required for the killing of cultured hepatocytes by hydrogen peroxide. Evidence for the participation of hydroxyl radicals formed by an iron-catalyzed Haber-Weiss reaction.