Efficient scavenging of fatty acid oxidation products by aminoguanidine

Lipid oxidation leads to the formation of reactive aldehydes that may play an important role in atherogenesis by altering the normal pathway of lipoprotein metabolism and by exerting toxic effects on vascular wall components. Recent studies indicate that advanced glycation end products, which form spontaneously from the reaction of reducing sugars with amino groups, may promote oxidative damage in vivo. Moreover, the pharmacological inhibitor of advanced glycation aminoguanidine has been shown to lower circulating low-density lipoprotein levels in human subjects and to inhibit certain oxidative reactions in vitro. To define more precisely the potential interaction of AG with oxidized lipids, we have studied and identified the major products that form from the reaction of AG with the oxidation products 4-hydroxynonenal and malondialdehyde. AG was found to be an efficient scavenger of alpha,beta-unsaturated aldehydes when compared to nucleophilic amino acids (Cys, Lys, His), suggesting that one of its mechanisms of action in vivo is to protect tissue constituents from the damaging effects of oxidative stress.