Importance of Locations of Iron Ions to Elicit Cytotoxicity Induced by a Fenton-Type Reaction

Abstract

The impact of the site of the Fenton reaction, i.e., hydroxyl radical (•OH) generation, on cytotoxicity was investigated by estimating cell lethality in rat thymocytes. Cells were incubated with ferrous sulfate (FeSO4) and hydrogen peroxide (H2O2), or pre-incubated with FeSO4 and then H2O2 was added after medium was replaced to remove iron ions or after the medium was not replaced. Cell lethality in rat thymocytes was estimated by measuring cell sizes using flow cytometry. High extracellular concentrations of FeSO4 exerted protective effects against H2O2-induced cell death instead of enhancing cell lethality. The pre-incubation of cells with FeSO4 enhanced cell lethality induced by H2O2, whereas a pre-incubation with a high concentration of FeSO4 exerted protective effects. FeSO4 distributed extracellularly or on the surface of cells neutralized H2O2 outside cells. Cytotoxicity was only enhanced when the Fenton reaction, i.e., the generation of •OH, occurred inside cells. An assessment of plasmid DNA breakage showed that •OH induced by the Fenton reaction system did not break DNA. Therefore, the main target of intracellularly generated •OH does not appear to be DNA.

Comparative Study of Porous Iron Foams for Biodegradable Implants: Structural Analysis and In Vitro Assessment

“…These results have shown that the cytotoxicity level mainly depends on ferrous ion concentrations released from the materials. Moreover, since it is well established that reactive oxygen species (ROS) are generated via the catalytic decomposition of hydrogen peroxide by ferrous ions leading to the Fenton reaction-mediated cell cytotoxicity [ 45 ], we presume that this phenomenon can be responsible for the cytotoxic effect induced by the tested materials. However, additional studies are required to confirm this assumption.…”

Ferroptosis, necroptosis and cuproptosis: Novel forms of regulated cell death in diabetic cardiomyopathy

“…Spontaneous lipid peroxidation is initiated by ROS, and intracellular soluble ROS, including superoxide, hydrogen peroxide, and hydroxyl radicals. Among these, hydroxyl radicals are the most active and toxic ROS (32), which can rob the hydrogen atoms of phosphorylated PUFAs and form peroxides (PUFA-PL-OOH), directly leading to the death of iron. We will describe this process by splitting and tracing.…”

Nanodiamond surface as a photoluminescent pH sensor

“…In contrast, the PLA is environmentally friendly, non-hazardous [28] and enables the control of the size, morphology, and shape of the NDs, which are metal-free [29]. The latter is especially essential for biomedical applications because metal impurities make chemically inert NDs deadly toxic because Fe impurities induce the production of highly cytotoxic hydroxyl radicals (HO  ) in the Fenton reaction of H 2 O 2 with Fe 2+ [30] leading to oxidative stress and damage of biomolecules involved in redox cycling in cells [31]. Moreover, both HPHT NDs and DNDs exhibit mainly hydrophobic properties and collapse into lumps in polar solvents, such as water or saline.…”