Original Contribution Nitric oxide as a cellular antioxidant: A little goes a long way

Nitric oxide (NO S ) is an effective chain-breaking antioxidant in free radical-mediated lipid oxidation (LPO). It reacts rapidly with peroxyl radicals as a sacrificial chain-terminating antioxidant. The goal of this work was to determine the minimum threshold concentration of NO S required to inhibit Fe 2+ -induced cellular lipid peroxidation. Using oxygen consumption as a measure of LPO, we simultaneously measured nitric oxide and oxygen concentrations with NO S and O2 electrodes. Ferrous iron and dioxygen were used to initiate LPO in docosahexaenoic acidenriched HL-60 and U937 cells. Bolus addition of NO S (1.5 AM) inhibited LPO when the NO S concentration was greater than 50 nM. Similarly, using (Z)-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate as a NO S donor we found that an average steady-state NO S concentration of at least 72 T 9 nM was required to blunt LPO. As long as the concentration of NO S was above 13 T 8 nM the inhibition was sustained. Once the concentration of NO S fell below this value, the rate of lipid oxidation accelerated as measured by the rate of oxygen consumption. Our model suggests that a continuous production of NO S that would yield a steady-state concentration of only 10–20 nM is capable of inhibiting Fe 2+ -induced LPO.