Radical Model of Arsenic(III) Toxicity: Theoretical and EPR Spin Trapping Studies

Abstract

Abstract Correspondence to: Frederick. Villamena@osumc.edu , Arsenic is one of the most environmentally significant toxins and a great global health concern. Long known for its acute toxicity, arsenic has also been discovered to be a potent carcinogen. Evidence links arsenic toxicity and carcinogenic actions to reactive oxygen species (ROS). In most animal including humans, arsenic undergoes a biomethylation to yield organic arsenic species, long assumed to be a process of detoxification. However, a growing body of evidence suggests that these organic arsenic species, particularly the reduced trivalent intermediates, may be just as if not more toxic than the inorganic analogs. Furthermore, current food safety regulations often monitor only inorganic arsenic levels. There is, therefore, a clear need for more literature and empirical data concerning the toxic mechanisms of arsenic.In this study, we examined organic and inorganic arsenites capacity to generate ROS when exposed to common oxidizing agents via EPR spectroscopy and spin-trapping with the cyclic nitrone 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Experimental observations were theoretically rationalized using density functional theory approach.

Genistein induces apoptosis in vitro and has antitumor activity against human leukemia HL‐60 cancer cell xenograft growth in vivo

“…The intrinsic apoptotic pathway is associated with mitochondrial functions for causing cytochrome c release and activation of caspase‐9, including mtROS . Numerous evidences have shown that ROS play a vital role in DNA damage, cellular apoptosis, tissue damage, and aging . Our results indicated that genistein increased ROS (Figure A) and decreased the levels of Δ Ψ m (Figure C) in HL‐60 cells, thus, we suggesting genistein induced cell apoptosis via ROS and mitochondria.…”

One-step selective hydroxylation of benzene to phenol with hydrogen peroxide catalysed by copper complexes incorporated into mesoporous silica–alumina

“…For example, the EPR spectrum of the HO • radial adduct (DMPO–OH) exhibits signals with a relative peak ratio of 1:2:2:1 with the hyperfine coupling constants of a N = a H = 14.9 G, whereas the EPR spectrum of the HO 2 • radical adduct affords more lines with hyperfine coupling constant of a N (13–14 G) which is significantly larger than a H (9–11 G). 28,37–41,47 Carbon-centred radical adducts afford a larger a H value than the a N value. 28,42 Thus, the type of radical species can be readily distinguished based on the hyperfine splitting pattern of the DMPO spin adducts.…”

Oxidative Balance in Brain After Exposure to Arsenic in Ex Vivo and in Vivo Models.

“…-tocopherol, -T) compounds; (2) prevention of radical formation (Halliwell, 1994), such as by ferritin (Ft) action chelating Fe; and (3) repair of already performed damage, such as by the activity of DNA repairing enzymes (Halliwell, 1994). Zamora et al (2014) examined the capacity of trivalent arsenic species arsenous acid (iAs(III)), monomethylarsonous acid (MMA(III)), and dimethylarsinous acid (DMA(III)) to generate ROS through a theoretical analysis of their structures, redox properties, and their reactivities to various ROS using a density functional theory approach and by employing electron paramagnetic resonance (EPR) techniques. Spin trapping studies showed a higher propensity for methylated arsenicals to generate radicals than iAs(III) upon treatment with H 2 O 2 .…”