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Cardiovascular Disease and Oxidative Stress
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Marco Fernandes, Alisha Patel, Holger Husi
The successive electron acquisition by the superoxide anion (O2·−), the primary form of ROS, and further interactions with other molecules either by metal- or enzyme-based catalyzed reactions leads to the production of secondary ROS (Valko et al., 2007). They can be classified as free radical species such as O2·−, the hydroxyl radical (·OH), and the hydroperoxy radical (HOO·), and in non-radical species such as the hydrogen peroxide (H2O2) and hypochlorite (ClO-) (Valko et al., 2007). Superoxide radicals can also interact with nitric oxide (NO) to yield, in a diffusion-controlled reaction, peroxynitrite (ONOO-), a very reactive intermediate with a relatively short half-life, which possesses a remarkable cytotoxic capacity against pathogens and concomitant deleterious functions in disease as an endogenous toxicant (Radi, 2013). Peroxynitrite belongs to the family of Reactive Nitrogen Species (RNS) are a family of antimicrobial molecules that are derived from NO and O2·−. RNS are produced by enzymatic activity of nitric oxide synthase 2 (NOS2) and NADPH oxidase. Nitric oxide is the considered the most prominent of the RNS family and is found in mitochondria (Bolisetty and Jaimes, 2013). Under physiological conditions, RNS are radicals that are involved in cellular signalling, vasodilation, and the body’s immune response (Ozcan and Ogun, 2015). Table 7.1 lists the most common RNS species, however only nitric oxide and nitrogen dioxide are free radicals, whereas peroxynitrite is not since NO and NO2 molecules are uncharged and contain an unpaired valence electron in the outer shell (Pacher et al., 2007).
Effects of green tea polyphenols against metal-induced genotoxic damage: underlying mechanistic pathways
Published in Journal of Toxicology and Environmental Health, Part B, 2023
María Del Carmen García-Rodríguez, Lourdes Montserrat Hernández-Cortés, Víctor Manuel Mendoza-Núñez, Francisco Arenas-Huertero
Reactive species are highly reactive molecules that contain reactive oxygen species (ROS) or nitrogen (RNS). These species include both FR and non-radical molecules that are involved in FR generation (Ye et al. 2015). FR possess an unpaired electron in their outermost orbital and are therefore highly unstable which capture electrons from other atoms, producing a chain reaction (Phaniendra, Jestadi, and Periyasamy 2015; Maddu 2019). Although reactive species are endogenously produced as a result of cellular metabolism, environmental factors such as exposure to metals might also contribute significantly to the production of ROS (Xu et al. 2017). Exposure to transition metal ions leads to in vivo production of ROS, RNS and FR due to their intra-cellular reduction The intracellular reduction of metals produces hydroxyl radical (•OH) through the Fenton reaction and Haber-Weiss cycle. This radical is one of the most biologically important ROS produced by metals, as it is highly reactive and is the radical most frequently responsible for damage to macromolecules (Valko et al. 2016). The attack of •OH on lipids might lead to a series of chain reactions that damage cell membranes and eventually result in cell death. Further, •OH oxidize nucleotide bases and form adducts that induce DNA damage (Jomova and Valko 2011; Valko et al. 2006). Metal-generated FR might also interfere with metabolic processes, disrupt functions of antioxidant enzymes, and alter the cell cycle and apoptosis (Tchounwou et al. 2012; Zhu and Costa 2020).