Feed-back inhibition of oxidative stress by oxidized lipid/amino acid reaction products.

Three oxidized lipid/amino acid reaction products (OLAARPs): 1-methyl-4-pentyl-1,4-dihydropyridine-3,5-dicarbaldehyde, 1-(5-amino-1-carboxypentyl)pyrrole, and N-(carbobenzyloxy)-1(3)-[1-(formylmethyl)hexyl]-l-histidine dihydrate, were prepared and tested for antioxidative activity in a microsomal system in order to investigate the effect that OLAARP formation may be playing in the oxidative stress process. The microsomal system consisted of freshly prepared trout muscle microsomes, which were oxidized in the presence of 5 microM Cu2+, 1 mM Fe3+/5 mM ascorbate, or 1 mM Cu2+/10 mM H2O2, and the compound to be tested as antioxidant added at 50 microM. At different periods of time, samples were tested for lipid peroxidation, assessed by the formation of thiobarbituric acid reactive substances (TBARS), and protein damage, which was evaluated by the formation of protein carbonyls and amino acid analysis. The three OLAARPs and butylated hydroxytoluene significantly (p < 0.05) protected against lipid peroxidation and protein damage for the three systems assayed. On the contrary, neither the amino acids used in the preparation of OLAARPs nor alpha-tocopherol, mannitol, aminoguanidine, or 4, 5-dihydroxy-1,3-benzenedisulfonic acid exhibited this constant protection. Because OLAARPs were produced at inhibitory levels during microsomal lipid peroxidation, these results suggest that OLAARP formation may be an antioxidative defense mechanism by which oxidative stress is feed-back-inhibited, delaying the damage caused by reactive oxygen species.