ABSTRACT
It has been shown that various nitric oxide donors and metabolites have similar effects on lipid peroxidation in rat myocardium homogenate. The formation of malondialdehyde, a secondary product of lipid peroxidation, was inhibited in a dose-dependent manner by PAPA/NONO (a synthetic nitric oxide donor), S-nitrosoglutathione, nitrite, and nitroxyl anion. The inhibition of lipid peroxidation was provided most efficiently by the administration of dinitrosyl-iron complexes with dextran and PAPA/NONO. S-nitrosoglutathione also inhibited the destruction of coenzymes Q9 and Q10 during free radical oxidation of myocardium homogenate. Low-molecular-weight dinitrosyl iron complexes with cysteine also promoted lipid peroxidation, which is probably due to iron release during the destruction dinitrosyl iron complexes. It is likely that the antioxidant action of nitric oxide derivatives is related to the reduction of ferry forms of hemoproteins and interaction of nitric oxide with lipid radicals.
Subject(s)
Antioxidants/pharmacology , Lipid Peroxidation/drug effects , Nitric Oxide Donors/pharmacology , Nitric Oxide/metabolism , Oxidants/pharmacology , Animals , Coenzymes/antagonists & inhibitors , Hydrazines/pharmacology , Iron/pharmacology , Male , Malondialdehyde/analysis , Myocardium/chemistry , Nitric Oxide/pharmacology , Nitrogen Oxides/pharmacology , Rats , Rats, Wistar , S-Nitrosoglutathione/pharmacology , Ubiquinone/analogs & derivatives , Ubiquinone/antagonists & inhibitorsABSTRACT
It has been established that albumin-bound dinitrosyl iron complexes can be destroyed by superoxide radicals generated in a xanthine-xanthine oxidase system. It was shown that peroxynitrite also effectively destroyed albumin-bound dinitrosyl iron complexes. At the same time, hydrogen peroxide and tert-butyl hydroperoxide did not stimulate the destruction of albumin-bound dinitrosyl iron complexes up to concentrations one order higher than the content of NO. The data have been obtained indicating that dinitrosyl iron complexes possess the vasodilatory activity. It has been proposed that peroxynitrite and superoxide radical, by causing the destruction of albumin-bound dinitrosyl iron complexes, affect the physiological properties of nitric oxide.
Subject(s)
Iron/chemistry , Nitrogen Oxides/chemistry , Reactive Oxygen Species/chemistry , Serum Albumin, Bovine/chemistry , Animals , Blood Pressure/drug effects , Iron/metabolism , Iron/pharmacology , Kinetics , Male , Nitric Oxide/chemistry , Nitrogen Oxides/metabolism , Nitrogen Oxides/pharmacology , Rats , Rats, Wistar , Serum Albumin, Bovine/pharmacologyABSTRACT
The interaction between glutathione-containing dinitrosyl iron complexes and superoxide radicals has been studied under the conditions of superoxide radical generation in mitochondria and in a model system xanthine-xanthine oxidase. It has been shown that both superoxide radical and hydroxyl radical are involved in the destruction of dinitrosyl iron complexes. At the same time, iron contained in dinitrosyl iron complex, apparently, does not catalyze the decomposition of hydrogen peroxide with the formation of hydroxyl radical. It has been found that dinitrosyl iron complexes with different anion ligands inhibit effectively the formation of phenoxyl probucol radical in a hemin-H2O2 a system. In this process, different components of the dinitrosyl iron complexes take part in the antioxidant action of these complexes.
