Interactions of nitric oxide with lipid peroxidation products under aerobic conditions: Inhibitory effects on the formation of malondialdehyde and related thiobarbituric acid-reactive substances

Under aerobic conditions, exposure of peroxidized lipids to nitric oxide (N O) was found to result in a rapid decrease in the levels of thiobarbituric acid-reactive substances (TEARS), Addition of 10-100 mu M NO to rat brain h omogenates preincubated for 2 h at 37 degrees C caused up to a 20% decrease in the levels of TEARS compared to controls. A similar inhibitory effect w as observed on TEARS produced by Fe2+-induced decomposition of 15-hydropero xyeicosatetraenoic acid (15-HPETE), due apparently to NO-induced decomposit ion of the hydroperoxide (ferrous oxidation/xylenol orange assay). Prostagl andin G(2) (PGG(2), 35 mu M), as a model bicyclic endoperoxide, and malondi aldehyde (MDA, 20 mu M), the main component of TEARS, proved also susceptib le to degradation by NO or NO donors (diethylamine NONOate, DEA/NO) at conc entrations of 100 mu M or higher in 0.05 M phosphate buffer, pH 7.4, and at 37 degrees C, as indicated by the reduced response to the TEA assay. No si gnificant effect on TEARS determination was caused by nitrite ions. These a nd other data indicate that NO can inhibit TEARS formation by decomposing p rimary lipid peroxidation products, chiefly 15-HPETE and related hydroperox ides, and, to a lesser extent, later stage TEARS precursors, including bicy clic endoperoxides and MDA, via nitrosation and other oxidative routes, wit hout however affecting chromogenic reactions during the assay. (C) 2000 Aca demic Press.