Redox active metal-induced oxidative stress in biological systems

Abstract

A number of studies performed on biological systems have shown that redox-active metals such as iron and copper as well as other transition metals can undergo redox cycling reactions and produce reactive free radicals termed also reactive oxygen species (ROS) or reactive nitrogen species (RNS). The most representative examples of ROS and RNS are the superoxide anion radical and nitric oxide, respectively, both playing a dual role in biological systems. At low/moderate concentrations of ROS and RNS, they can be involved in many physiological roles such as defense against infectious agents, involvement in a number of cellular signaling pathways and other important biological processes. On the other hand, at high concentrations, ROS and RNS can be important mediators of damage to biomolecules involving DNA, membrane lipids, and proteins. One of the most damaging ROS occurring in biological systems is the hydroxyl radical formed via the decomposition of hydrogen peroxide catalyzed by traces of iron, copper and other metals (the Fenton reaction). The hydroxyl radical is known to react with the DNA molecule, forming 8-OHGuanine adduct, which is a good biomarker of oxidative stress of an organism and a potential biomarker of carcinogenesis. This review discusses the role of iron and copper in uncontrolled formation of ROS leading to various human diseases such as cancer, cardiovascular disease, and neurological disorders (Alzheimer's disease and Parkinson's disease). A discussion is devoted to the various protective antioxidant networks against the deleterious action of free radicals. Metal-chelation therapy, which is a modern pharmacotherapy used to chelate redox-active metals and remove toxic metals from living systems to avoid metal poisoning, is also discussed.

In vitro and in vivo toxicity assessment of nanoparticles

“…ROS formation is one of the mechanisms for nanoparticle toxicity [14,15]. Interaction of nanoparticles with cells induces pro-oxidant effects leading to ROS generation, mitochondrial respiration and NADPH-dependent enzyme systems [16][17][18]. Upon internalization of nanoparticles, phagocytosis induces the production of reactive oxygen species ROS [17][18][19].…”

Fenton chemistry at aqueous interfaces

“…The characteristic multiplet patterns arising from natural abundance 35 Cl (75%) and 37 Cl (25%) chlorine isotopes let us establish the number of Cl − contained in each detected species and, hence, the molecular composition of these singly charged ions ( -in bulk water (7), we estimate that less than 0.1% Fe 2+ should have been consumed under present conditions. In other words, reactions R3a and R4 proceed ∼10…”

“…The bactericidal action of antibiotics has been linked to their ability to induce Fenton chemistry in vivo (9,(30)(31)(32)(33)(34). Oxidative damage from exogenous Fenton chemistry likely is responsible for acute and chronic pathologies of the respiratory tract (35)(36)(37)(38).…”

Deep UV generation and direct DNA photo-interaction by harmonic nanoparticles in labelled samples

“…18,34,38,39 As for classical phototherapy, these approaches can generate major side effects due to the presence of toxic compounds and ROS which can diffuse to nearby tissues generating oxidative stress. 40,41 The approach proposed, based on nonlinear optical response by HNPs and direct photo-interaction with nuclear DNA, might avoid side effects due to organic ligands and diffusion of toxic compounds, increasing selectivity and treatment localization. Moreover, the activation of the process is intrinsically limited to femtosecond-pulse excitation and cannot be obtained with any other artificial or natural light source, differently also from the approaches based on sequential up-conversion of light frequency.…”