Scavenging of lipid peroxyl radicals protects plasma lipids and proteins from peroxynitrite

Peroxynitrite can be produced in the vasculature from a superoxide anion reaction with nitric oxide. A surplus of peroxynitrite in the intravascular compartment is a common feature of several chronic diseases. The development of pharmacological modalities that interfere with the formation of peroxynitrite or inhibit its oxidative damage may be of utility for the prevention and/or treatment of several pathologies. Our previous investigations showed that catalytically inactivating peroxynitrite-derived free radicals with tempol or scavenging reactive aldehyde species with phenelzine protects the blood plasma and platelets from the oxidative damage of peroxynitrite. However, the degree of inhibition of the cytotoxic effects of peroxynitrite using tempol or phenelzine was modest. In the present study, the aim was to examine if scavenging lipid peroxyl radicals with U-83836E can achieve superior protection from peroxynitrite. This was assessed by treating blood plasma or platelets with 100 µM peroxynitrite alone or in combination with U-83836E, and then measuring the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation as indices of lipid peroxidation and protein oxidation, respectively. It was observed that scavenging lipid peroxyl radicals with 75-100 µM U-83836E increasingly reversed protein carbonylation induced by peroxynitrite in blood plasma and platelets, in addition to TBARS formation in blood plasma. These findings are further discussed in the context of the mechanisms by which U-83836E may protect against the cell-damaging effects of peroxynitrite.