RESUMEN
The hemolytic activity of new spatially screened hybrid antioxidants--ichfans--has been studied. The concentration-dependent hemolytic action of high concentrations of ichfans with 8, 10, 12 or 16 carbon atoms in the aliphatic chain has been revealed. A nonmonotonic dependence of the hemolytic activity on the hydrophobic properties of ichfans has been found.
Asunto(s)
Antioxidantes/farmacología , Fenoles/farmacología , Compuestos de Amonio Cuaternario/farmacología , Antioxidantes/química , Hemólisis/efectos de los fármacos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Técnicas In Vitro , Fenoles/química , Compuestos de Amonio Cuaternario/química , Relación Estructura-ActividadRESUMEN
Morphological transformation of erythrocytes and structural changes in the erythrocyte membrane have been revealed by scanning electron microscopy and spin-probe technique. These effects were caused by the incorporation of ichphans, new generation drugs combining antioxidant and anticholinesterase effects, into the erythrocyte membrane and their distribution in the intramembrane space. Different distribution and modulatory effect of the derivatives with different hydrophobic properties have been shown. The derivatives with 8 and 10 carbon atoms in the aliphatic substituent were the most efficient modifiers of the membrane structure and morphology of erythrocytes.
Asunto(s)
Antioxidantes/farmacología , Membrana Celular/efectos de los fármacos , Membrana Celular/ultraestructura , Eritrocitos/efectos de los fármacos , Fenoles/farmacología , Compuestos de Amonio Cuaternario/farmacología , Animales , Antioxidantes/química , Células Cultivadas , Eritrocitos/ultraestructura , Membrana Dobles de Lípidos/metabolismo , Espectroscopía de Resonancia Magnética , Estructura Molecular , Fenoles/química , Compuestos de Amonio Cuaternario/química , Ratas , Relación Estructura-ActividadRESUMEN
The influence of new hybrid antioxidants ichphans on the structure of liposome lipid bilayer was studied. The analysis of the kinetics of the ascorbate-induced reduction of spin probe radical centers incorporated in a membrane revealed that ichphans produce a modifying effect on the structure of liposome membrane. It was established that derivates with distinct hydrophobic properties transform different sites of the membrane that are the sites of localization of ichphans in the intramembraneous space. The data obtained suggest that lipid components play an important role in the effects of ichphans on biological membranes.
Asunto(s)
Antioxidantes/química , Ácido Ascórbico/química , Membrana Dobles de Lípidos/química , Fenoles/química , Compuestos de Amonio Cuaternario/química , Espectroscopía de Resonancia por Spin del Electrón , Liposomas/química , Oxidación-Reducción , Marcadores de SpinRESUMEN
The method of spin probe and scanning electron microscopy were used to study the effects of some new synthetic antioxidants and bioregulators, the derivatives of 5-hydroxybenzimidazole, on the membrane structure and morphology of erythrocytes. Analysis of EPR spectra and electron micrographs revealed that the derivatives with various side substituents affect the membrane structure and shape of erythrocytes in a concentration-dependent manner, the effect correlating with the hydrophobic properties of the side derivatives. It was shown that all the compounds in the concentration range 1.10(-7) - 1.10(-3) M exhibit the echinocytogenic action, the most profound effect being found in the compound with benzyl- and ethoxygroup in sites 2 and 5, respectively. Our data suggest that nonelectrolytes, the derivatives of 5-hydroxybenzimidazole, are located in the outer monolayer of erythrocyte membrane.
Asunto(s)
Antioxidantes/farmacología , Bencimidazoles/farmacología , Eritrocitos/ultraestructura , Animales , Forma de la Célula/efectos de los fármacos , Espectroscopía de Resonancia por Spin del Electrón , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/ultraestructura , Eritrocitos/efectos de los fármacos , Técnicas In Vitro , Masculino , Microscopía Electrónica de Rastreo , Ratas , Marcadores de SpinRESUMEN
Scanning electron microscopy was used to study the effects of the new generation of compounds ICHFANs, which have a combined antioxidant and acetylcholine esterase inhibitory effect on the surface architectonics of erythrocytes. The incorporation of each of the studied compounds with the positively charged quaternary ammonium in the erythrocyte membrane and their distribution in the itramembraneous space were accompanied by the formation of echinocytes, stomatocytes, and compensative effects on erythrocyte shape. The time-dependent morphological transformation of erythrocytes apparently is determined by changes in the distribution of the compounds between the outer and inner monolayers of the erythrocyte membrane. A difference in the morphological effects of compounds with different hydrophobic properties was revealed.
Asunto(s)
Antioxidantes/farmacología , Forma de la Célula/efectos de los fármacos , Eritrocitos/efectos de los fármacos , Fenoles/farmacología , Compuestos de Amonio Cuaternario/farmacología , Animales , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/ultraestructura , Eritrocitos/citología , Eritrocitos/ultraestructura , Técnicas In Vitro , Microscopía Electrónica de Rastreo , Ratas , Relación Estructura-ActividadRESUMEN
The capacity of erythrocyte membranes for organic nonelectrolytes from different chemical groups of chemical compounds was studied by the spin probe method and scanning electron microscopy. Hydrophobic spin-labeled derivatives of gamma-carbolin and stearic acid and the screened phenol antioxidant fenozan-1 were used as nonelectrolytes. Based on the analysis of electron spin resonance spectra of the hydrophobic spin-labeled nonelectrolytes and electron micrographs of erythrocytes, differences in the capacity of distribution regions in the intramembrane space of the derivative of gamma-carbolin and fenozan-1, on the one hand, and the spin-labeled derivative of fatty acid, on the other hand, were found. The first group has at least two membrane distribution regions, whereas in the second case only one type of distribution was found. The influence of limited membrane capacity on the realization of biological activity of organic nonelectrolytes is discussed.
Asunto(s)
Membrana Eritrocítica/metabolismo , Compuestos Orgánicos/sangre , Electrólitos/sangre , Espectroscopía de Resonancia por Spin del Electrón , HumanosRESUMEN
The effect of regulatory peptide thyrotropin-releasing hormone (TRH) on the structure of the plasma membrane and morphology of rat erythrocytes was studied using a spin probe and scanning electron microscopy. EPR spectra of the spin probe introduced in the intramembrane space demonstrate that TRH at 10(-7) and 10(-3) M induces structural changes in the erythrocyte membrane. Scanning electron microscopy showed that introduction of TRH at 10(-11), 10(-7), and 10(-3) M in the erythrocyte suspension increased the proportion of discocytes as compared to the control. This effect is due to TRH-induced cell transformation in discocytes. The obtained data suggest that TRH affects the membrane structure and the morphology of erythrocytes, changes the functional activity of these cells and, thus, indirectly influences the rate of the oxygen supply to tissue.
Asunto(s)
Eritrocitos/efectos de los fármacos , Hormona Liberadora de Tirotropina/farmacología , Animales , Relación Dosis-Respuesta a Droga , Espectroscopía de Resonancia por Spin del Electrón , Membrana Eritrocítica/efectos de los fármacos , Membrana Eritrocítica/ultraestructura , Eritrocitos/ultraestructura , Microscopía Electrónica de Rastreo , RatasRESUMEN
Scanning electron microscopy revealed changes in erythrocyte morphology induced by the synthetic antioxidant phenozan-1. Phenozan-1 at 10(-7)-10(-5) M acts as an echinocytogen. This effect of the antioxidant is, probably, due to its distribution in the external monolayer of the erythrocyte membrane and associated structural changes.