The hydroxylamine OXANOH and its reaction product, the nitroxide oxano ., act as complementary inhibitors of lipid peroxidation

Abstract

The effects of the nitroxide 2-ethyl-2,5,5-trimethyl-3-oxazolidinoxyl (OXANO .) and the corresponding hydroxylamine 2-ethyl-1-hydroxy-2,5,5-trimethyl-3-oxazolidine (OXANOH) on in vitro lipid peroxidation in rat liver microsomes and reconstituted lipid vesicles were investigated, and compared with those of some commonly used spin trapping agents. OXANO . and OXANOH (10–100 μM) inhibited iron-dependent lipid peroxidation, as did the spin trapping agents (10–100 mM). OXANO . mainly inhibited the rate of peroxidation, but caused only a small delay in the time of onset. OXANOH exerted its effect by delaying the onset of peroxidation in an antioxidant fashion, and also by inhibiting the rate. Higher concentrations of both substances were required to inhibit t-butylhydroperoxide-dependent lipid peroxidation. OXANO . was found to oxidize the ferrous-ADP complex required for initiation of peroxidation, and this is probably the basis of the inhibitory effect of this compound. Since the reaction of OXANO . tends to produce OXANOH and vice versa, either one could inhibit all reactions of lipid peroxidation.