There has been recent interest in the administration of superoxide dismutase (SOD) for ablation of oxygen mediated tissue damage. It is known that oxygen radicals such as superoxide and hydroxyl radical are important radiolysis products in an oxygenated aqueous environment. To date, there is no means of easily studying the effects of augmenting SOD cells. We have found that certain nitroxides, particularly oxazolidine containing nitroxides, may act as low molecular weight, cell permeable, superoxide dismutase mimics. We have demonstrated pH dependence of the oxazolidine nitroxide (OXANO) SOD mimic in both a Xanthine oxidase and cesium source superoxide generating systems. Similarly, the rates of SOD like activity of the oxan system has been determined. The scope of the chemistry is being investigated by synthesizing analogues. Likewise, the biochemistry of the reaction is under investigation. We have shown that these compounds protect mammalian cells in vitro against hydrogen peroxide and hypoxanthine,/xanthine oxidase cytotoxicity. The compounds have been demonstrated to be non-toxic and capable of penetrating intracellular sites. We have recently demonstrated that nitroxides are also radiation protectors for mammalian cells and preliminary work indicates that they protect against whole body radiation in mice. Preliminary studies also indicate that nitroxides can have a marked influence on the cytotoxicity mediated by a number of chemotherapy drugs.
