Diabetes Mellitus, Type 2
© Springer-Verlag Berlin Heidelberg 2014. All rights are reserved.Free radicals possess at least one unpaired electron in the outer electron orbit and usually, but not always, are highly chemically reactive. Molecular dioxygen (O2) is stable; however, the oxygen-centered free radicals, superoxide (O2•-) and hydroxyl (•OH), are not stable. In biological systems, reactive oxygen species (ROS), such as superoxide (O2•-) and hydrogen peroxide (H2O2), play important signaling roles but may also contribute to cellular damage and disease development. Nitric oxide (also known as nitrogen oxide, or nitrogen monoxide, or simply NO) is also a free radical, and the existence of an unpaired electron may be reflected by the use of the abbreviation NO• rather than NO. Unless discussing the three-redox forms of nitrogen monoxide (the nitrosonium ion, NO+, the uncharged free radical, NO•, and the nitroxyl anion, NO- or HNO), the abbreviation NO will be used throughout this chapter. Reactive nitrogen species (RNS) are produced in biological systems starting with the reaction of NO with O2•- to form the highly reactive RNS peroxynitrite (ONOO-) that, unlike NO or O2•-, is a very strong oxidant and nitrating agent. Thus, despite both NO and O2•- being free radicals, neither are as reactive as ONOO-, and the toxicity of these two free radicals relates primarily to ONOO-. Understanding how ONOO- modulates different intracellular biochemical pathways and how this may affect normal physiological processes and/or give rise to pathological conditions is an emerging area of great scientific interest. ONOO- exerts its adverse effects by direct interaction with CO2, proteins that contain transition metal centers or thiols, or indirectly by aiding the generation of the highly potent hydroxyl radical. In this chapter, we outline the biochemistry and pathophysiology of ONOO- with a particular reference to cardiovascular disease and diabetes. We also address how scavenging strategies can attenuate the toxic effects of ONOO- and therefore may repress the pathophysiological effects of ONOO- and offer the potential for new therapeutic interventions.
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