Antioxidant actions of nitroxyl (HNO)

Nitrogen oxides are endogenously produced signaling/effector molecules that have the potential to both cause and ameliorate oxidative stress. Whether nitrogen oxides behave as oxidants or antioxidants is dependent on many factors including the cellular environment, the concentration, and the presence of other reactive species. To date, the nitrogen oxide nitroxyl (HNO) has only been reported to possess prooxidant properties. However, some of its chemical properties would predict that it could also serve as an antioxidant. In this study, the possible antioxidant actions of HNO were examined using the yeast Saccharomyces cerevisiae model system. The effect of HNO on membrane lipid peroxidation was examined and HNO was determined to act solely as an antioxidant in this system. In the presence of glutathione, a thiol-containing peptide that scavenges HNO, the antioxidant action was decreased. In addition, the antioxidant properties of HNO were not due to the conversion of HNO to NO. These results were also confirmed with in vitro assays of oxidative stress. Thus, HNO has the potential to preserve lipid membrane integrity by its antioxidant actions.