Inhibition of lipid peroxidation in synaptosomes and liposomes by nitrates and nitrites.

NO is produced endogenously from arginine by the action of NO synthase, and exogenously by nitrovasodilators, including organic nitrates and nitrites. NO has been proposed as a cytotoxic and cytoprotective agent. There is strong evidence that NO acts as an apparent antioxidant in inhibiting lipid peroxidation, via chain termination, and interestingly lipid nitrates and nitrites have been proposed to be products of this chain termination. Both pro- and antioxidant mechanisms may be drawn for nitrates and nitrites; therefore, their effects on lipid peroxidation were measured in two systems, using tocopherol, thiol, and an NO donor for comparison: (1) rat cerebrocortical synaptosomes with Fe(II)-induced lipid peroxidation measured by thiobarbituric acid reactive substances (TBARS), and (2) phospholipid liposomes with an azo-initiator induction system, quantified by a fluorescent probe of peroxide formation. In contrast to the classical nitrate nitroglycerin, novel nitrates which release NO on reaction with thiols and two novel nitrates which spontaneously generate NO in aqueous solution inhibited lipid peroxidation. i-Amyl nitrite inhibited lipid peroxidation, and its properties were further studied with ESR spectroscopy. The data show that classical nitrites and novel nitrates are not prooxidants, but inhibit lipid peroxidation.