Free radicals reactive nitrogen species

Chronic inflammatory states associated with infection or xenobiotic chemical exposure from the environment can produce genomic lesions that, in time, can become initiated tumors. It is known that hosts do fight microbial infections by moderate production of various free radicals reactive oxygen species (ROS) [e.g., hydroxyl radical (OH ) and the superoxide radical (OT)] or reactive nitrogen species (RNS) [e.g., nitric oxide (NO ) and the strong oxidant, peroxynitrite (ONOO )]. Within limits inflammatory signaling pathways of the host can control excessive free radical concentrations by means of enzymes such as NADPH oxidase, myeloperoxidase, nitric oxide synthase, and others (Federico et al. 2007 Rakoff-Nahonm 2006). 

Fig. 4.1 Free radicals (reactive oxygen species and reactive nitrogen species)...

Reactive nitrogen species are another factor of free radical damage in rheumatoid arthritis, although their role is less studied than that of oxygen radicals. Stichtenoth and Frolich [242] pointed out that the inhibition of nitric oxide synthesis had beneficial effects in humans. Mazzetti et al. [243] found that IL-1(3 stimulated NO production in RA chondrocytes. We demonstrated that NO synthase of RA neutrophils generated the enhanced amount of peroxynitrite [234]. Nitric oxide and oxygen radicals are also important inducers of death of human osteoarthritic synoviocytes [244]. 

Free radical (FR) processes have been of condiderable interest for medical science in the last few decades. Chemiluminescent methods have been found to be suitable for the detection of reactive oxygen species (ROS) and reactive nitrogen species.1 These methods are sensitive, fast, and make it possible to follow the development of the process. 

The fleeting intermediates produced by radiation and respiration are called free radicals. We discussed them briefly in Chapter 1. Later in the book, we will refer to free radicals many times. 1 use the term rather loosely for convenience. Not all of these fleeting intermediates are free radicals within the usual definition of the term. Applying the correct terminology, however, is cumbersome. Another umbrella term, reactive oxygen species, is even more cumbersome and also untrue — not all are especially reactive and some, such as nitric oxide (NO) are technically reactive nitrogen species. A third possible term, oxidants, is also incorrect ... 

A free radical is an atom or molecule that possesses one or more unpaired electrons. Since electrons are more stable when paired together in orbitals, radicals are generally unstable and are therefore highly reactive with a variety of substrates. Free radicals of importance in biological systems include reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS include superoxide anion hydroxyl radical ("OH),... 

Many questions still remain, such as whether extracellular Ap modulates intracellular Ap, or the mechanism by which Ap accumulation leads to synaptic dysfunction. Other factors, such as oxidative stress, which is extensive in AD, may aid the early accumulation of Ap (Butterfield et al., 2(X)2b). AP peptides stimulate oxidative stress by direct and indirect mechanisms. AP-induced oxidative stress may result from an imbalance between reactive oxygen species (ROS) and reactive nitrogen species (RNS), which could react with a number of cellular macromolecular targets including proteins, lipids, carbohydrates, DNA, and RNA. An early marker for oxidative stress is the formation of protein carbonyls, 4-hydroxy-2-tra 5-nonenal (4-HNE) and 3-nitrotyrosme (3-NT), a marker for the nitration of proteins (Butterfield, 2002). Ap peptide can bind to mitochondrial proteins to generate free radicals, or it can promote oxidative stress via neuroinflanunation. Ap peptides stimulate microglial cells to release a neurotoxin, quinoUnic acid, which may also play a role in neurotoxicity (Guillemin et al., 2003). 

A superoxide free radical (Of) is produced from an enzyme called NADPH oxidase mostly in mitochondrion (Rios-Arrabal et al, 2013). It is less reactive than a hydroxyl radical (OH), but much more selective. Its lifetime is not longer than few seconds in biological systems, and it reacts with another superoxide molecule (self-dismutation reaction) to form a hydrogen peroxide. Superoxide also reacts with a nitric oxide to form a peroxynitrite, a very potent oxidant that belongs to reactive nitrogen species (RNS) (Juranek et al, 2013 Kalyanaraman, 2013 Miguel, 2010 Sahin Basak and Candan, 2013). 

In a simplified way, oxidants can be classified as free-radical and non-radical species (cf Table 3 adapted from [30]). They are often classified as reactive oxygen species (ROS) and reactive nitrogen species (RNS). Although the latter, similarly to ROS, contain oxygen atom(s) - for example, NO NO", and NO Cl - the RNS usually participate at nitrosylation reactions. 

---