Superoxide anion radical sources

Noda Y, Anzai K, Mori A, Kohno M, Shinmei M and Packer L. 1997. Hydroxyl, end superoxide anion radical scavenging activities of natural source antioxidants using the computerized JES-FR30 ESR spectrometer system. Biochem Mol Biol Int 42(1) 35—44. 

An example of free radical formation is molecular oxygen, which can accept electrons from a variety of sources to produce reactive oxygen species (ROS) such as the superoxide radical, the hydroxyl radical, and the nitric oxide radical. The superoxide anion radical is formed when one electron is taken up by one of the 2p orbitals of molecular oxygen. Certain drugs and other xenobiotics have the capacity to undergo so-called redox cycles, whereby they provide electrons to molecular oxygen and form super oxide. 

The respiratory chain is the major source of oxygen free radicals. In theory, molecular oxygen should be completely reduced in complex IV by four electrons from water without the formation of intermediates. In practice, sometimes partial reduction occurs with oxygen being converted to superoxide anion radicals (Fig. 15.1). Also, the ubiquinone reactions in complexes I and II have an unfortunate tendency to leak electrons directly to oxygen. Overall, up to 2% of cellular oxygen forms superoxide free radicals and the body has developed defence mechanisms to counter their damaging effects. 

TABLE 1 Reaction sources of superoxide anion radical (O )... 

As mentioned above, mitochondria are major cellular sources of oxyradicals. Superoxide anion radical (O ), generated upon autoxidation of ubisemiquinone, is vectorially released into the inter membrane space and the mitochondrial matrix. In the latter compartment, Oj dismutates to HjOj. 

Exposure to cadmium may produce oxidative stress, which may result directly in toxicity or may occur secondary to cadmium toxicity. Results from studies using cultured cells have demonstrated cadmium-induced formation of superoxide anion radicals (Amoruso et al. 1982) and implicated superoxide anions in Cd-induced DNA single-strand scissions (Ochi et al. 1983). Cadmium inhibited superoxide dismutase in vivo, resulting in elevated superoxide levels (Shukla et al. 1987). Cadmium has been shown to increase peroxidation of lipids in isolated rat hepatocytes (Stacey et al. 1980) and in other target tissues in vivo and in vitro (Gabor et al. 1978 Wahba and Waalkes 1990) thus, increased levels of lipid peroxides following exposure to cadmium could constitute a source of active oxygen species. 

One of the important consequences of neuronal stimulation is increased neuronal aerobic metabolism which produces reactive oxygen species (ROS). ROS can oxidize several biomoiecules (carbohydrates, DNA, lipids, and proteins). Thus, even oxygen, which is essential for aerobic life, may be potentially toxic to cells. Addition of one electron to molecular oxygen (O,) generates a free radical [O2)) the superoxide anion. This is converted through activation of an enzyme, superoxide dismurase, to hydrogen peroxide (H-iO,), which is, in turn, the source of the hydroxyl radical (OH). Usually catalase... 

Other postulated routes (Jourd heuil et al., 2003) to RSNO formation include the reaction between NO and 02 to yield N02 via a second-order reaction. NO and thiolate anion, RS, react giving rise to thiyl radical, (RS ) [e]. RS then reacts with NO to yield RSNO [f]. The reaction between RS and RS- can also be the source of non-enzymatic generation of superoxide anion (02 ) [g], [h]. 02 reacts with NO to produce peroxynitrite (ONOO ) [i] (Szabo, 2003). Thiols react with ONOOH to form RSNOs [k] (van der Vliet et al.,1998). 

The majority of the enzyme-catalyzed reactions discussed so far are oxidative ones. However, reductive electron transfer reactions take place as well. Diaphorase, xanteneoxidase, and other enzymes as well as intestinal flora, aquatic, and skin bacteria—all of them can act as electron donors. Another source of an electron is the superoxide ion. It arises after detoxification of xenobiotics, which are involved in the metabolic chain. Under the neutralizing influence of redox proteins, xenobiotics yield anion-radicals. Oxygen, which is inhaled with air, strips unpaired electrons from these anion-radicals and gives the superoxide ions (Mason and Chignell 1982). 

The primary quantum yields ranged between 5 x 10 3 and 8 x 10 3 [11], In oxygenated media solvated electrons (eaq) are mainly trapped by molecular oxygen, generating hydrogen peroxyl radicals and superoxide anions this disproportionation is a source of hydrogen peroxide and thereby hydroxyl radicals. 

---