Nitric oxide (NO) mediates diverse physiological processes in living organisms. Small molecular NO donors usually lack stability and have a short half-life in human tissues, limiting the therapeutic application. The anionic tetranitrosyl iron complex with thiosulfate ligands (TNIC) is one of the most promising NO donors. This study shows that bovine serum albumin (BSA) can effectively stabilize the TNIC complex under aerobic (physiological) conditions, which contributes to its prolonged action as NO donor. Our results demonstrated that TNIC-BSA inhibits formation of TBARS - standard biomarker for the lipid peroxidation induced oxidative stress. Also, it was found that TNIC-BSA inhibits the catalytic activity of mitochondrial membrane-bound enzymes: cytochrome c oxidase and monoamine oxidase A. Together, these results demonstrate that, stabilization of TNIC with BSA opens up the possibility of its practical application in chemotherapy of socially significant diseases.
Iron , Lipid Peroxidation/drug effects , Mitochondria , Nitrogen Oxides , Serum Albumin, Bovine , Thiosulfates , Animals , Brain/cytology , Iron/chemistry , Iron/pharmacology , Mice , Mitochondria/drug effects , Mitochondria/enzymology , Mitochondria/metabolism , Monoamine Oxidase/metabolism , Nitrogen Oxides/chemistry , Nitrogen Oxides/pharmacology , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/pharmacology , Thiosulfates/chemistry , Thiosulfates/pharmacology
The antioxidant and antiradical properties of the tetra nitrosyl iron complex with thiosulfate ligands (TNIC) were studied in vitro in mouse brain homogenates. It was found for the first time that TNIC is an effective antioxidant. The effect of TNIC on the catalytic activity of mitochondrial enzymes cytochrome c oxidase and monoamine oxidase A was studied. It was shown for the first time that TNIC is an inhibitor of the catalytic activity of cytochrome c oxidase and monoamine oxidase A in animal brain mitochondria in vitro.
Brain/enzymology , Electron Transport Complex IV , Iron , Mitochondria/enzymology , Mitochondrial Proteins , Monoamine Oxidase Inhibitors , Nitrogen Oxides , Thiosulfates , Animals , Electron Transport Complex IV/antagonists & inhibitors , Electron Transport Complex IV/metabolism , Iron/chemistry , Iron/pharmacology , Mice , Mitochondrial Proteins/antagonists & inhibitors , Mitochondrial Proteins/metabolism , Monoamine Oxidase/metabolism , Monoamine Oxidase Inhibitors/chemical synthesis , Monoamine Oxidase Inhibitors/chemistry , Monoamine Oxidase Inhibitors/pharmacology , Nitrogen Oxides/chemical synthesis , Nitrogen Oxides/chemistry , Nitrogen Oxides/pharmacology , Thiosulfates/chemical synthesis , Thiosulfates/chemistry , Thiosulfates/pharmacology
We studied membranotropic properties of NO donor 2-nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine and its structural analog succinate 3-hydroxy-6-methyl-2-ethylpyridine (Mexidol). It was shown that the compounds under study are incorporated into modeled membranes and form long-living complexes with pyrene in the region of fatty acid tails of phospholipids. Luminol-amplified chemiluminescence analysis showed that both compounds exhibited antiradical activity and in a concentration of 0.1 mM reduced chemiluminescence intensity by more than 70%. 2-Nitroxysuccinate 3-hydroxy-6-methyl-2-ethylpyridine inhibited catalytic activity of monoamine oxidase A more efficiently than its structural analogue Mexidol.
Antioxidants/pharmacology , Cell Membrane/drug effects , Free Radicals/metabolism , Lipid Peroxidation/drug effects , Animals , Cell Membrane/enzymology , Cell Membrane/metabolism , Heart , Liposomes/chemistry , Luminescent Measurements , Male , Mice , Mice, Inbred C57BL , Monoamine Oxidase/drug effects , Monoamine Oxidase/metabolism , Myocardium/chemistry , Myocardium/metabolism , Phosphatidylcholines/chemistry , Phosphatidylcholines/metabolism , Picolines/chemistry , Picolines/pharmacology
The neuroprotective action of hybrid structures based on fullerene C60 with attached proline amino acid has been studied. Hybrid structures contained natural antioxidant carnosine or addends with one or two nitrate groups. It has been shown that all studied compounds had antioxidant activity and decreased the concentration of malondialdehyde in homogenates of the rat brain. Compound 1, which contained the antioxidant carnosine, has been found to be the most effective antioxidant. All compounds except IV and V inhibited the activity of monoamine oxidase B, while compounds I-IV increased the activity of monoamine oxidase A. All investigated compounds inhibited glutamate-induced Ca2+ uptake into synaptosomes of the rat brain cortex. Compound III, containing two nitrate groups, has been found to be the most effective inhibitor. This compound caused a significant increase of the currents of AMPA receptors (AMPA, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid).
Antioxidants/pharmacology , Brain/drug effects , Fullerenes/pharmacology , Neuroprotective Agents/pharmacology , Animals , Antioxidants/chemistry , Brain/cytology , Brain/enzymology , Brain/metabolism , Calcium/metabolism , Fullerenes/chemistry , In Vitro Techniques , Lipid Peroxidation/drug effects , Malondialdehyde/metabolism , Mitochondria/drug effects , Mitochondria/enzymology , Molecular Structure , Monoamine Oxidase/metabolism , Neuroprotective Agents/chemistry , Rats , Receptors, AMPA/metabolism , Synaptosomes/drug effects , Synaptosomes/metabolism
