Organic Nitrites and NO:  Inhibition of Lipid Peroxidation and Radical Reactions

Abstract

Organic nitrites, such as i-amyl nitrite (IAN), are nitrovasodilator drugs used both clinically and recreationally. Nitrites are also chemically reasonable biological products of NO metabolism, in particular in both inhibition of lipid peroxidation by NO and induction of lipid peroxidation by peroxynitrite and NO2. Nitrites are also potential products of biomolecule nitrosation and intermediates in biotransformation of nitrate vasodilators. Although mechanisms can be drawn for both prooxidant and antioxidant activity, IAN has been observed to inhibit lipid peroxidation in a variety of systems. To test if the antioxidant activity of nitrites results from NO release alone, inhibition of lipid peroxidation was studied for four organic nitrites and four NO donor NONOates. Iron-induced lipid peroxidation in synaptosomal tissue homogenates and azo compound-initiated lipid peroxidation in liposomes and linoleic acid SDS comicelles were examined. Lipid peroxidation was quantified by TBARS and oxygen uptake analysis. A good correlation of rate of NO release with IC50 for inhibition of lipid peroxidation was observed for the NONOates, compatible with lipid radical chain termination by NO, for which a chain termination stoichiometry of 0.4-0.5 mol of lipid peroxyl radicals per mole of NO was determined. In neutral aqueous solution, nitrites also spontaneously released NO as measured by chemiluminescence; however, no correlation was observed between the rate constants of NO release for the nitrites and their inhibitor potency toward lipid peroxidation. Long chain nitrites were seen to be relatively good inhibitors of lipid peroxidation by mechanisms that must involve factors in addition to simple homolysis to release NO. Evidence for direct alpha-hydrogen atom abstraction from the nitrite by peroxyl radicals was obtained by analysis of aldehyde products and supported by MO calculations. The data suggest that lipid nitrites formed as NO chain termination products have the capacity to further inhibit lipid peroxidation and to release NO.

The potent vasodilator ethyl nitrite is formed upon reaction of nitrite and ethanol under gastric conditions

“…In blood the half-lives of alkyl nitrites are in the range of seconds (isobutyl nitrite around 1.4 min) [44], and they can decompose by nonenzymatic hydrolysis as well as by enzymatic cleavage. In the case of ethyl nitrite it is known that it spontaneously releases low fluxes of • NO in aqueous solution [45] by homolytic cleavage of the O-NO bond [46].The inhibition of vascular relaxation in the presence of ODQ and the inability of L-NAME to block the vasodilatory effect, strongly suggest that the relaxation was caused by • NO from ethyl nitrite. One might argue that ethanol and nitrite produced these effects independently of ethyl nitrite formation, since vasoactivity has been described for both these compounds [47,48].…”

Stabilizing Oils from Smoked Pink Salmon (Oncorhynchus gorbuscha)

“…Among these components, phenols have demonstrated antioxidant capabilities (Pearson and Gillett 1996). Nitrites are also known to inhibit lipid peroxidation by participating in the radical‐quenching process (Nicolescu and others 2004). The peroxidation process can also be inhibited by formate anion, which is a radical scavenger found in smoke flavorings and smoke‐processed meats (Schwanke and others 1996; Coronado and others 2002).…”

Escherichia colicellular responses to exposure to atmospheric‐pressure dielectric barrier discharge plasma‐treated N‐acetylcysteine solution

“…; Laskey and Mathews ; Kalyanaraman ; Nicolescu et al . ). Another possibility for not detecting the lipid peroxidation may be the higher permeability of peroxynitrite compared with ROS in plasma‐treated NAC solution.…”

“…The main source of intracellular nitrosative stress is reported as peroxynitrite (Szabo ; Nicolescu et al . ; Pacher et al . ).…”