RESUMO
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.
Assuntos
Ferro , Peroxidação de Lipídeos/efeitos dos fármacos , Mitocôndrias , Óxidos de Nitrogênio , Soroalbumina Bovina , Tiossulfatos , Animais , Encéfalo/citologia , Ferro/química , Ferro/farmacologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Monoaminoxidase/metabolismo , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/farmacologia , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacologia , Tiossulfatos/química , Tiossulfatos/farmacologiaRESUMO
It was shown for the first time that pentaamino acid derivative of fullerene C60 (potassium salt of fullerenylpenta-N-dihydroxytyrosine) affects three targets of type 2 diabetes mellitus. It competitively inhibits the enzymes aldose reductase and sorbitol dehydrogenase and also has an antiglycation effect on bovine serum albumin. The inhibition constants for these enzymes were calculated.
Assuntos
Aldeído Redutase/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/química , L-Iditol 2-Desidrogenase/química , Aldeído Redutase/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , L-Iditol 2-Desidrogenase/metabolismo , CamundongosRESUMO
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.
Assuntos
Encéfalo/enzimologia , Complexo IV da Cadeia de Transporte de Elétrons , Ferro , Mitocôndrias/enzimologia , Proteínas Mitocondriais , Inibidores da Monoaminoxidase , Óxidos de Nitrogênio , Tiossulfatos , Animais , Complexo IV da Cadeia de Transporte de Elétrons/antagonistas & inibidores , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Ferro/química , Ferro/farmacologia , Camundongos , Proteínas Mitocondriais/antagonistas & inibidores , Proteínas Mitocondriais/metabolismo , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/síntese química , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Óxidos de Nitrogênio/síntese química , Óxidos de Nitrogênio/química , Óxidos de Nitrogênio/farmacologia , Tiossulfatos/síntese química , Tiossulfatos/química , Tiossulfatos/farmacologiaRESUMO
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.
