RESUMEN
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.
Asunto(s)
Hierro , Peroxidación de Lípido/efectos de los fármacos , Mitocondrias , Óxidos de Nitrógeno , Albúmina Sérica Bovina , Tiosulfatos , Animales , Encéfalo/citología , Hierro/química , Hierro/farmacología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/enzimología , Mitocondrias/metabolismo , Monoaminooxidasa/metabolismo , Óxidos de Nitrógeno/química , Óxidos de Nitrógeno/farmacología , Albúmina Sérica Bovina/química , Albúmina Sérica Bovina/farmacología , Tiosulfatos/química , Tiosulfatos/farmacologíaRESUMEN
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.
Asunto(s)
Encéfalo/enzimología , Complejo IV de Transporte de Electrones , Hierro , Mitocondrias/enzimología , Proteínas Mitocondriales , Inhibidores de la Monoaminooxidasa , Óxidos de Nitrógeno , Tiosulfatos , Animales , Complejo IV de Transporte de Electrones/antagonistas & inhibidores , Complejo IV de Transporte de Electrones/metabolismo , Hierro/química , Hierro/farmacología , Ratones , Proteínas Mitocondriales/antagonistas & inhibidores , Proteínas Mitocondriales/metabolismo , Monoaminooxidasa/metabolismo , Inhibidores de la Monoaminooxidasa/síntesis química , Inhibidores de la Monoaminooxidasa/química , Inhibidores de la Monoaminooxidasa/farmacología , Óxidos de Nitrógeno/síntesis química , Óxidos de Nitrógeno/química , Óxidos de Nitrógeno/farmacología , Tiosulfatos/síntesis química , Tiosulfatos/química , Tiosulfatos/farmacologíaRESUMEN
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.
