RESUMEN
A number of pyridincarboxylic acid derivatives PV-1-4, 7 and emoxypine preparation antioxidative activity in yolk lipoprotein suspension was studied by a method of Fe(2+)-initiated biochemiluminescence. Lipid peroxidation in suspension was effectively inhibited by the studied compounds in various concentration ranges. PV 1, 3, 4, 7 inhibited lipid peroxidation at the concentrations 100-fold, then those of PV 2 and emoxypine. Antiradical activity of the studied compounds was demonstrated by their forming a complex with the stable diphenylpickrylhydrazyl radical. The effect of these compounds as antioxidants is discussed.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Antioxidantes/farmacología , Ácidos Carboxílicos/farmacología , Depuradores de Radicales Libres/farmacología , Ácidos Carboxílicos/química , Hierro/metabolismo , Peroxidación de Lípido , Mediciones Luminiscentes , Mutación , Piridinas/químicaRESUMEN
Interaction of alpha-tocopherol and 1,4-dihydropyridine with endoplasmic reticulum membranes and model systems, human serum albumin and phospholipid bilayer, was studied using the microcalorimetry and fluorescent probes procedures. Dependence of microviscosity changes in the endoplasmic reticulum membranes on the place of antioxidants localization (protein structures or phospholipid phase) was shown. Increase of membrane structuralization under the influence of 1,4-dihydropyridines blocked their antioxidant action in spontaneous and induced lipid peroxidation.
Asunto(s)
Antioxidantes/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Membranas Intracelulares/efectos de los fármacos , Nifedipino/farmacología , Nitrendipino/farmacología , Calorimetría , Colorantes Fluorescentes , Humanos , Membrana Dobles de Lípidos , Peroxidación de Lípido/efectos de los fármacos , Vitamina E/farmacologíaRESUMEN
Antiradical and antioxidative activities of dieton, phoridon, niphedipin, phlamicar, mildronat in vitro were studied by spectrophotometer's method with the use of dyfenilpycrilgydrasil and method of pulse voltametry. Also influence of drugs was studied under antioxidative insufficiency (AOI), which had modelled by exclusion of alpha-tocopherol from the animal's ration.
Asunto(s)
Antioxidantes/farmacología , Depuradores de Radicales Libres/farmacología , Plantas/química , Animales , Antioxidantes/aislamiento & purificación , Dihidropiridinas/química , Dihidropiridinas/farmacología , Electroquímica , Depuradores de Radicales Libres/aislamiento & purificaciónRESUMEN
Antiradical activity and ability to interaction with phosphatidylcholine bilayer of the physiological active compounds (PhAC), concerning the classes of phenylalkilamines (dobutamine, verapamil), dihydro pyridines (BAY-K-4688, nifedipine), analogues of crown ether (carbicyle, diol) was studied. By means of the method of microcalorimetry and spectrophotometry it was shown the complexing ability PhAC with the phospholipid bilayer of the model membrane. It was stated the simbasity in the changes of the thermal effect of the compounds with the negative inotropic activity during its reaction with phosphatidylcholine bilayer and antiradical activity. That show on the presence of antiradical component in the mechanism that compounds' action.
Asunto(s)
Agonistas de los Canales de Calcio/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Cardiotónicos/farmacología , Depuradores de Radicales Libres/farmacología , Miocardio/metabolismo , Vasodilatadores/farmacología , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/química , Ácido 3-piridinacarboxílico, 1,4-dihidro-2,6-dimetil-5-nitro-4-(2-(trifluorometil)fenil)-, Éster Metílico/farmacología , Calcio/farmacocinética , Agonistas de los Canales de Calcio/química , Bloqueadores de los Canales de Calcio/química , Cardiotónicos/química , Dobutamina/química , Dobutamina/farmacología , Depuradores de Radicales Libres/química , Transporte Iónico/efectos de los fármacos , Membrana Dobles de Lípidos , Nifedipino/química , Nifedipino/farmacología , Relación Estructura-Actividad , Vasodilatadores/química , Verapamilo/química , Verapamilo/farmacologíaRESUMEN
Interaction of phenol type antioxidants and Ca-channel blockers, derivatives of 1,4-dihydropyridines, with rat liver microsomes has been studied in vitro by means of spectrophotometry and fluorescent probes using ANS and polymethine dye 4501 u. Incubation of microsomes in the absorption spectra of the antioxidant results in changes of structure dynamic parametres of microsomal membranes, and in changes of their microviscosity and in surface state modification. The mechanism of microsomal action was different for phenol type antioxidants and for 1,4-dihydropyridines and depended on the radical structure. Ability of Ca-channel blockers and verapamil to interact with microsomal membrane protein structures was shown.
Asunto(s)
Antioxidantes/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Dihidropiridinas/farmacología , Membranas Intracelulares/efectos de los fármacos , Microsomas Hepáticos/efectos de los fármacos , Fenoles/farmacología , Animales , Técnicas In Vitro , Microsomas Hepáticos/ultraestructura , Ratas , Espectrofotometría UltravioletaRESUMEN
As a result of experiments carried out on adult (6-8 months) and old (24-26 months) male rats of the Wistar line it is established that emotional-pain stress results (in one day) in essential increase in the activity of spontaneous, NADPH--and ascorbate-dependent peroxidation of lipids in the liver microsomes, which is expressed in the old animals rather than in the adult ones. The induced peroxidation of lipid six days after the stress effect remains activated in the adult rats and decreases to the control level in the old ones. Accumulation of lipoperoxidation products in the membrane structure of hepatocytes is accompanied by the changes of physico-chemical parameters of microsomal membranes, microviscosity and surface potential in particular. Availability of conformational shifts of membrane proteins of microsomes under the conditions of lipoperoxidation activation evoked by the stress is accompanied by changes of physico-chemical parameters of microsomal membranes. Changes in the membrane structure are expressed to the less extent in the microsomes of old rats liver as well, that evidences for the age-dependent differences of adaptational capacities of the organism.
Asunto(s)
Envejecimiento/metabolismo , Retículo Endoplásmico/metabolismo , Peroxidación de Lípido/fisiología , Hígado/metabolismo , Estrés Fisiológico/metabolismo , Adaptación Fisiológica , Animales , Fenómenos Químicos , Química Física , Masculino , Membranas/metabolismo , Microsomas Hepáticos/metabolismo , Ratas , Ratas WistarRESUMEN
Results obtained from the study of the interaction between the phytosteroid preparation (BTK-8L) and fractionated rat liver nuclear chromatin under conditions of the tetrachloromethane and chlorophos intoxications are described. It is shown that preventive injection of BTK-8L to the animals has a partial protective effect on transcriptionally active and repressed liver chromatin. This preparation interacts with chromatin histone proteins binding with them and changes the nucleoprotein complex structure as a results of which the chromatin fraction components become less accessible to the damaging action of tetrachloromethane and chlorophos. The BTK-8L protective effect is exhibited on the DNA replication and transcriptional levels under conditions of tetrachloromethane and chlorophos intoxications.
Asunto(s)
Antioxidantes/uso terapéutico , Intoxicación por Tetracloruro de Carbono/tratamiento farmacológico , Cromatina/efectos de los fármacos , Esteroides/uso terapéutico , Triclorfón/envenenamiento , Animales , Proteínas Cromosómicas no Histona/efectos de los fármacos , ADN/efectos de los fármacos , Etidio , Colorantes Fluorescentes , Histonas/efectos de los fármacos , Masculino , Ratas , Ratas Wistar , Transcripción Genética/efectos de los fármacosRESUMEN
Results of the study of interaction of the phytoecdysteroid preparation (BTK-8L) with fractionated rat liver nuclear chromatin were described. It was shown that the interaction resulted in the "loosening" of the histone proteins structure both in active and repressed chromatin. At the same time the reparative DNA synthesis in the repressed fraction was stimulated. The Change revealed might be the basis of protective properties of BTK-8L as to chromatin at chloro and organophosphorus intoxications.
Asunto(s)
Cromatina/metabolismo , Hígado/efectos de los fármacos , Esteroides/farmacología , Animales , ADN/efectos de los fármacos , Hígado/metabolismo , Masculino , Conformación de Ácido Nucleico , Conformación Proteica , Ratas , Ratas WistarRESUMEN
Interaction of antioxidant (derivatives of phenol and 1,4-dihydropyridine) with bilayer from lecithin was studied by means of electronic spectroscopy and microcalorimetry. The connection of warm effects and spectral properties was estimated by chemical structure of antioxidants. The effect of physiologically active compounds on the structural and dynamic parameters of the bilayer was determined by means of fluorescent probing.
Asunto(s)
Antioxidantes/química , Membrana Dobles de Lípidos/química , Fosfatidilcolinas/química , Calorimetría , Dihidropiridinas/química , Estructura Molecular , Fenoles/química , Espectrofotometría Ultravioleta , Propiedades de SuperficieRESUMEN
Genoprotective effect of preparation BTK-8L from plant steroids at prophylactic injection to experimental animals at chromatin damage by chlorofos was revealed. Antioxidant action of the preparation, being most highly expressed in the transcriptionally active chromatin fraction, is, probably, the most likely mechanism of the action. The realization of this action might be carried out as a result of the direct binding of BTK-8L with the chromatin protein-lipid complex, which was revealed during the analysis of the model systems showing binding of the preparation with chromatin fractions in vitro. Correction of structural chromatin organization and its transcriptional activity modified with intoxication of animals by chlorofos may occur as a result of such binding. Genoprotective properties in BTK-8L correlate to some extent with the lowering of the death rate of experimental animals at the early stage of intoxication by chlorofos at the prophylactic injection of the preparation, which, nevertheless, was not so significant, as in the case of intoxication by tetrachloromethane. Such fact allowed suggesting the existence of delayed unfavourable consequences for the organism (mutagenesis, cancerogenesis) as a result of the realization of the genotoxic action of chlorofos.
Asunto(s)
Antimutagênicos/farmacología , Antioxidantes/farmacología , Cromatina/efectos de los fármacos , Plantas Medicinales , Esteroides/farmacología , Triclorfón/antagonistas & inhibidores , Animales , Intoxicación por Tetracloruro de Carbono/prevención & control , Masculino , Ratas , Ratas Wistar , Transcripción Genética/efectos de los fármacos , Triclorfón/envenenamientoRESUMEN
Hepatoprotective action of prophylactic injection of aqueous solution of preparation BTK-8L from plant ecdysteroids to experimental animals with the liver damage by tetrachloromethane was revealed. This effect at least partially was connected with the genoprotective action of the given preparation. As a result, normalization of free radical chromatin lipid peroxidation reaction, modified at the intoxication, as well as partial correction of physical and chemical properties of chromatin protein-lipid complex were those molecular mechanisms of genoprotective action of BTK-8L, which were manifested by the influence of the preparation on such indices which characterized the depth structure of the complex as microviscosity and energy transfer from the protein to the lipid probe. Investigation of the interaction of the preparation with chromatin fractions in vitro and comparison of this interaction with the analogous process in model systems allowed revealing determinative participation of chromatin proteins and lipids in the given process. The preparation interacted more intensively with the active chromatin fraction, which contained a more marked protein-lipid complex, as comparing to the repressed one. Injection of the preparation also normalized such indices as relation between the chromatine fractions and protein/DNA ratio in them. On the contrary, injection of the alcoholic solution of the preparation to experimental animals, aggravated genotoxic tetrachloromethane action.
Asunto(s)
Antimutagênicos/farmacología , Intoxicación por Tetracloruro de Carbono/prevención & control , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Cromatina/efectos de los fármacos , Esteroides/farmacología , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Radicales Libres , Genoma , Peroxidación de Lípido/efectos de los fármacos , Masculino , Plantas Medicinales , Ratas , Ratas WistarRESUMEN
Vincapane, apressin, raunatin, reserpine and prazosin have been studied for their effect on the state of microviscosity of phospholipid bilayers from lecithin and cardiolipine. The method of fluorescent probing using pyrene and asymmetrical polymethine dye 4501 u have been used for this study. Character of changes of phospholipid bilayers microviscosity as affected by these compounds depends on their concentration in the solution. Vincapan lowers microviscosity of membranes from lecithin in the interval of the concentrations given. Advantages of fluorescent probing by means of asymmetric polymethine dye in comparison with pyrene were shown.
Asunto(s)
Antihipertensivos/farmacología , Cardiolipinas , Membrana Dobles de Lípidos , Membranas Artificiales , Fosfatidilcolinas , Colorantes Fluorescentes , Espectrometría de Fluorescencia , ViscosidadRESUMEN
Physico-chemical parameters of membranes of skeletal muscles' sarcoplasmic reticulum in antioxidant insufficiency, which was modelled by excluding alpha-tocopherol from the animals ration, and after treatment with phenol antioxidant ionol were studied. It was shown that activation of lipid peroxidation in vitamin E insufficiency results in a significant lowering of microviscosity of lipid bilayer membranes of sarcoplasmic reticulum. Using polarography significant changes in membrane protein conformation were revealed, which were characterized by lowering of integrity and by disorganization of protein globules. Treatment of animals with antioxidant insufficiency with ionol led to certain normalization of changes of physico-chemical characteristics of the learned membrane structures caused by lipid peroxidation.
Asunto(s)
Antioxidantes , Músculos/efectos de los fármacos , Peróxidos/farmacología , Retículo Sarcoplasmático/efectos de los fármacos , Animales , Hidroxitolueno Butilado/farmacología , Membrana Celular/química , Membrana Celular/efectos de los fármacos , Femenino , Membrana Dobles de Lípidos , Peroxidación de Lípido , Músculos/metabolismo , Polarografía , Ratas , Ratas Endogámicas , Retículo Sarcoplasmático/metabolismo , Espectrofotometría UltravioletaRESUMEN
Interaction of cardiotonic drugs (strophantidine acetate, suphan, para-oxybenzoic acid) and ubiquinone with phospholipid bilayers has been studied. Exothermic effect of the reaction followed by an increase in microviscosity and hydrophobicity of the bilayer from cardiolipin, but by a decrease of the microviscosity of the bilayer from lecithin has been estimated. A correlation is observed between changes in the lecithin bilayer fluidity and the heat effect of the interaction at the initial period of time after mixing of reagents.