Oxidative Stress

ROS include a variety of oxygen containing substances with high reactivity with other biomolecules. ROS include both free radicals (containing one or more unpaired electrons), such as superoxide anion (O2-), hydroxyl ('OH), peroxyl (RO2'), and hydroperoxyl (HO2') radicals, and nonradical species that are either easily converted into radicals or are oxidizing agents, such as hydrogen peroxide (H2O2) and other peroxides (ROOH). Under physiologic conditions, ROS are produced in a controlled manner and play important roles as secondary messengers in many intracellular signaling pathways [16, 17]. However, excessive production of ROS under pathophysiologic conditions, namely oxidative stress, results in tissue damage.

The principal ROS made by cells is superoxide anion, generated by a single electron donation to molecular oxygen. Superoxide exerts a range of pathophysio-logic effects, such as induction of cell proliferation, apoptosis, and vasoconstriction. Superoxide has a relatively short half life and is cell-membrane impermeable; thus, it is unlikely to mediate effects distant from where it is produced. Many other ROS and reactive nitrogen species are formed secondary to reactions involving superoxide. Superoxide is rapidly dismutated to hydrogen peroxide. Hydrogen peroxide is lipid-soluble, has a longer biologic lifespan than superoxide, and crosses cellular membranes [17]. Hydroxyl radical could arise from superoxide and hydrogen peroxide. The hydroxyl radical is a highly reactive oxidant that has a very short half-life.

Oxidative stress is increasingly being recognized to operate as a main pathophys-iologic mechanism underlying aging and a large number of diseases, including cancer, neurodegenerative diseases, vascular diseases, and ED.

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