RESUMEN
The effect of the synthetic biguanide derivatives N-[imino(1-piperidinyl)methyl]guanidine (NIPMG) and 1,3-dimethyl-5-[(carbamimidamidomethanimidoil) amino]benzoyl-1,3dicarboxylate (DCB) on the degree of proteins oxidative modification (POM) and the DNA fragmentation, the content of the lipid peroxidation primary products - conjugated dienes (CD), and the activity of glutathione antioxidant system in the liver and heart of rats with experimental hyperglycemia was investigated. Administration of the biguanides (15.0 mg/kg) to hypoglycemic rats promoted reduction of the free radical processes intensity in the studied tissues. Data about CD and POM level changes in hyperglycemic rats treated by NIPMG and DKB correlate with the results of DNA fragmentation degree evaluation. At the same time, the activity of antioxidant enzymes (glutathione peroxidase and glutathione reductase), and the reduced glutathione content in the liver and heart of rats changed toward control values. For metformin, which was used as a comparison drug, changes in the studied parameters in the same direction were also found. These results indicate the ability of the tested biguanide derivatives to exhibit a positive regulatory effect on free radical homeostasis, reducing the degree of oxidative stress at this pathology.
Asunto(s)
Biguanidas/farmacología , Hiperglucemia/tratamiento farmacológico , Hígado/metabolismo , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Animales , Hiperglucemia/metabolismo , Hiperglucemia/patología , Hígado/patología , Masculino , Miocardio/patología , RatasRESUMEN
The effect of biologically active additive with immunomodulator properties epiphamine on the activity of antioxidant (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase) and NADPH-generating (glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) enzymes has been investigated at experimental cerebral ischemia/reperfusion in rats. The results obtained indicate epiphamine-induced changes of these enzymes activities towards control values. Changes in the content of lactate, a marker of the pathology development, have also been found in experimental animals under ischemia and epiphamine administration caused changes similar to those observed in the case of enzyme activities studied. In most cases, the changes were dose-dependent. Thus, epiphamine can be of considerable interest from the point of view of metabolic changes pharmacological correction at the development of the pathology accompanied by oxidative stress.
Asunto(s)
Isquemia Encefálica , Animales , Antioxidantes , Catalasa , Glutatión , Glutatión Peroxidasa , Glutatión Reductasa , NADP , Estrés Oxidativo , Ratas , Superóxido DismutasaRESUMEN
Melaxen administration to rats with brain ischemia/reperfusion was accompanied by a decrease of the lactate level (an organ ischemia marker), biochemiluminescence parameters characterizing the intensity of free radical processes and total antioxidant activity, the content of lipid peroxidation products, activity of superoxide dismutase and catalase, as compared with the values determined in rats with induced brain ischemia/reperfusion. Activity of aconitate hydratase, a sensitive target of free radicals action, and the citrate level in the brain and blood serum of melaxen-treated animals changed towards control values of intact animals. It is assumed that the effect of melaxen is associated with implementation of the antioxidant and protective properties of melatonin, the melaxen constituent, under conditions of post-ischemic reperfusion injury, accompanied by oxidative stress development.
Asunto(s)
Antioxidantes/farmacología , Encefalopatías , Encéfalo/metabolismo , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión , Animales , Encefalopatías/tratamiento farmacológico , Encefalopatías/metabolismo , Masculino , Ratas , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismoRESUMEN
It was studied the total antioxidant activity, content of primary lipid peroxidation (LPO) products and reduced glutathione, and the activity of glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and NADP-isocitrate dehydrogenase in rat tissues under phenylethyl biguanide (phenfor- min) action on the background of experimental brain ischemia/reperfusion development. It is stablished the analyzed parameters, increasing under ischemia/reperfusion conditions in the brain and blood serum of animals, exhibit a decrease upon the introduction of this biguanide derivative. The obtained data can be explained by a decrease in degree of mobilization of the antioxidant system--in particular, of its glutathione chain--in the pathologic state. Hence, there is a need in NADPH supply for the system functioning compared with the pathology. Thus, phenylethyl biguanide demonstrates its antioxidant and protective properties under oxidative stress development that is accompanied by accumulation of the products of free radical oxidation of biomolecules during the ischemic brain injury.
Asunto(s)
Antioxidantes/farmacología , Lesiones Encefálicas , Glutatión/metabolismo , Fenformina/farmacología , Daño por Reperfusión , Animales , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/metabolismo , Radicales Libres/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Oxidorreductasas/metabolismo , Ratas , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismoRESUMEN
The influence of melatonin on the reduced glutathione content, activity of glutathione peroxidase, glutathione reductase, and glutathione transferase in blood serum, heart, liver, and skeletal muscle of rats under conditions of experimental rheumatoid arthritis development has been estimated. A change in these parameters toward normal control values under the action of hormone has been revealed. The results can be related to realization of the melatonin antioxidant and protective properties under conditions of oxidative stress accompanying the development of rheumatoid arthritis.
Asunto(s)
Antioxidantes/metabolismo , Artritis Reumatoide , Glutatión/sangre , Melatonina/farmacología , Oxidorreductasas/sangre , Animales , Artritis Reumatoide/sangre , Artritis Reumatoide/tratamiento farmacológico , Modelos Animales de Enfermedad , Masculino , RatasRESUMEN
The effect of 3,5-dicarbomethoxyphenylbiguanide, which was selected with the Prediction of Activity Spectra of Substances (PASS) computer program, on the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione transferase in the heart and the blood serum of rats with experimental rheumatoid arthritis was investigated. The studied parameters changed towards control values when the tested compound was injected in animals with the pathology. These results can be explained by the cardioprotective and antioxidant activity of the compound. The data obtained during the study may be used for the development of new preventive and therapeutic agents for the treatment of the rheumatoid arthritis.
Asunto(s)
Antioxidantes/química , Guanidinas/química , Oxidorreductasas/química , Animales , Activación Enzimática , RatasRESUMEN
Treatment with the complex preparation containing pantogam, succinic acid, and chitosan normalized the concentration of reduced glutathione and activities of glutathione peroxidase, glutathione reductase, and some NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and NADPH-isocitrate dehydrogenase) in animals with experimental hypoxia/reperfusion of the brain. These results can be explained by suppression of free radical oxidation and normalization of the antioxidant system related to the neuroprotective, antihypoxic, and antioxidant properties of these substances, their involvement into the regulation of cell metabolism under pathological conditions accompanied by oxidative stress.
Asunto(s)
Isquemia Encefálica/complicaciones , Quitosano/farmacología , Glutatión/metabolismo , Ácido Pantoténico/análogos & derivados , Daño por Reperfusión/tratamiento farmacológico , Succinatos/farmacología , Ácido gamma-Aminobutírico/análogos & derivados , Animales , Quitosano/administración & dosificación , Combinación de Medicamentos , Radicales Libres/metabolismo , Glucosafosfato Deshidrogenasa/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Isocitrato Deshidrogenasa/metabolismo , Masculino , NADP/metabolismo , Estrés Oxidativo/fisiología , Ácido Pantoténico/administración & dosificación , Ácido Pantoténico/farmacología , Ratas , Daño por Reperfusión/etiología , Succinatos/administración & dosificación , Ácido gamma-Aminobutírico/administración & dosificación , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
The administration of chitosan succinate and N-succinylchitosan to rats with cerebral ischemia/reperfusion model damage leads to a decrease in the level of lactate (marker of ischemic injury development), parameters of biochemiluminescence (measure of free-radical oxidation intensity), and lipid peroxodation products in animal tissues as compared to untreated (pathologic) control. The obtained results show evidence of the ability of tested drugs to decrease the degree of oxidative stress manifestation under cerebral ischemia/reperfusion conditions, which is related to the positive control effect of chitosan-based drugs on the free-radical homeostasis.
Asunto(s)
Isquemia Encefálica/metabolismo , Quitosano/farmacología , Daño por Reperfusión/metabolismo , Succinatos/farmacología , Animales , Química Encefálica/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Modelos Animales de Enfermedad , Radicales Libres/metabolismo , Masculino , Oxidación-Reducción/efectos de los fármacos , Ratas , Daño por Reperfusión/tratamiento farmacológicoRESUMEN
The propagation of the pandemic influenza virus H1N1 in cultures of bronchial (Calu-3) and intestinal (Caco-2) differentiated epithelial cells of human origin was studied. The canine epithelial cell lines, MDCK-H and MDCK-2, were comparatively tested. The two human cell lines were found to be highly sensitive to the influenza pandemic strains A/Hamburg/05/09 and A/Moscow/501/2011 and maintained their replication without addition of trypsin to culture medium. Virus strains of seasonal influenza H1N1, such as A/Moscow/450/2003, A/Memphis/14/96, and laboratory strain A/PR/8/34, multiplied in these human cells in similar manner. The intracellular cleavage HA0-->HA1+HA2 by the host virus-activating protease (IAP) occurred in both human cell lines under infection with each influenza virus H1N1 including pandemic ones. Comparatively, this cleavage of all influenza H1N1 virus strains appeared to be either undetectable or low-detectible in MDCK-H and MDCK-2, respectively, thereby implying low levels of active IAP in these cells. Multiplication of pandemic and seasonal influenza H1N1 viruses in Calu-3 and Caco-2 cells caused cytopathic effect, which was accompanied with low autophagy and apoptosis events. These data allow recommending human cell lines, Calu-3 and Caco-2, for optimized isolation and passaging of clinical strains of Influenza pandemic viruses H1N1.
Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/fisiología , Gripe Humana/epidemiología , Gripe Humana/metabolismo , Pandemias , Replicación Viral/fisiología , Animales , Células CACO-2 , Efecto Citopatogénico Viral/fisiología , Perros , Humanos , Células de Riñón Canino Madin DarbyRESUMEN
During the winter 2009 outbreak in the Moscow Region, H3N2 influenza viruses were isolated from the nasopharyngeal washes of patients via their propagation in the human intestinal (Caco-2) and bronchial (Calu-3) epithelial cell cultures maintaining the proteolytic cleavage of HA0--> HA1+HA2 and multicycle virus replication. Analysis of the nucleotide sequences of virus RNA indicated that the 2009 viruses differed from those isolated in 2003 in 14 and 21 amino acids of the neuraminidase (NA) and hemagglutinin (HA) genes, respectively. The NA gene was 1762 nucleotides long whereas the 2003 isolates had a deletion of 66 nucleotides (22 amino acids) in the stalk region (short-stalk NA genotype) of viruses. The NA gene of the 2009 and 2003 isolates possessed an amino acid profile characterized for oseltamivir- and zanamivir-susceptible viral strains. The HA gene of the 2009 viruses contained an N-glycosylation site at Asn181 (an analog to Asn 65 numbering from a signal peptide), which correlated with the long-stalk NA gene. The 2009 viruses had Phe209 in the HA receptor binding center whereas the 2003 isolates possessed Ser209, which correlated with their differences in HA activity. Phylogenetic analysis showed that the NA genes of the 2003 and 2009 Moscow strains were located in the same genetic clade with a single common precursor while their HA genes were diverged in more genetic distance and located in different clades. Viral distribution in the phylogenetic tree indicated that the Moscow strains isolated in 2009 were not direct ancestors of those isolated in 2003; and during the period of 2003 to 2009, H3N2 influenza virus with a short-stalk NA genotype was substituted for a migrant virus possessing a long-stalk NA gene.
Asunto(s)
Evolución Molecular , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H3N2 del Virus de la Influenza A/genética , Gripe Humana/virología , Neuraminidasa/genética , Proteínas Virales/genética , Secuencia de Bases , Células CACO-2 , Humanos , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/genética , Moscú , Mutación Missense , Filogenia , ARN Viral/genética , Alineación de SecuenciaRESUMEN
AIM: Analysis of clinical cases of tick-borne spotted fever (TSF) group rickettsiosis in 2005 - 2010. MATERIALS AND METHODS: General clinical, biochemical and serological parameters were determined in 10 tick-borne spotted fever group rickettsiosis patients who had visited various geographical regions of the World. RESULTS: TSF group rickettsiosis diagnostic criteria, optimal serological diagnostics timing were determined. Possible diagnostic errors, features of serological diagnostics and antibacterial therapy of this nosologic form are discussed. CONCLUSION: Indication for TSF examination are primarily epidemiologic including tick attachment indication and clinical data. Serological studies are positive only in 3 - 4 weeks after the onset of the infection and thus can not be used for early diagnostics.
Asunto(s)
Fiebre Botonosa/diagnóstico , Fiebre Botonosa/inmunología , Enfermedades Transmisibles Emergentes/diagnóstico , Enfermedades Transmisibles Emergentes/inmunología , Viaje , Adulto , Animales , Fiebre Botonosa/tratamiento farmacológico , Enfermedades Transmisibles Emergentes/tratamiento farmacológico , Femenino , Humanos , Ixodes/microbiología , Masculino , Persona de Mediana Edad , Moscú/epidemiología , Rickettsia conorii/inmunología , Rickettsia conorii/aislamiento & purificaciónRESUMEN
We studied the effects of dimethoxyphenyl biguanide on glutathione peroxidase and glutathione reductase activities, level of reduced glutathione in rat tissues, and activity of some NADPH-regenerating enzymes (glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase) under conditions of ischemia-reperfusion of the brain. Administration of this biguanide derivative under pathological conditions led to a decrease in the analyzed parameters (elevated under conditions of ischemia-reperfusion) in the serum and brain tissue. The results attest to less pronounced mobilization of the glutathione system (compared to pathological state) due to antioxidant and protective properties of 2,4-dimethoxyphenyl biguanide under conditions of ischemic tissue damage associated with oxidative stress.
Asunto(s)
Antioxidantes/farmacología , Biguanidas/farmacología , Isquemia Encefálica/enzimología , Encéfalo/enzimología , Glutatión Peroxidasa/metabolismo , Glutatión Reductasa/metabolismo , Daño por Reperfusión/enzimología , Animales , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Isquemia Encefálica/sangre , Isquemia Encefálica/metabolismo , Glucosafosfato Deshidrogenasa/sangre , Glucosafosfato Deshidrogenasa/metabolismo , Glutatión/sangre , Glutatión/metabolismo , Glutatión Peroxidasa/sangre , Glutatión Reductasa/sangre , Isocitrato Deshidrogenasa/sangre , Isocitrato Deshidrogenasa/metabolismo , Masculino , Oxidación-Reducción , Ratas , Daño por Reperfusión/sangre , Daño por Reperfusión/metabolismoRESUMEN
The effect of citrate free-radical oxidation intensity and aconitate hydratase, superoxide dismutase and catalase activities in liver and blood serum of rats with experimental toxic hepatitis has been investigated. Citrate administration to rats with hepatitis decreased biochemiluminescence parameters and conjugated diene content in rats tissues, increased under conditions of CCl4-induced liver damage. At the same time aconitase activity, decreased at the pathology, increases. The superoxide dismutase and catalase activities increased in at experimental toxic hepatitis, tended towards control values after citrate administration.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Ácido Cítrico/metabolismo , Hepatitis Animal/metabolismo , Aconitato Hidratasa/metabolismo , Animales , Antioxidantes/farmacología , Intoxicación por Tetracloruro de Carbono/metabolismo , Catalasa/metabolismo , Ácido Cítrico/farmacología , Radicales Libres/metabolismo , Peroxidación de Lípido , Hígado/metabolismo , Mediciones Luminiscentes , Oxidación-Reducción , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
The purification and comparative characterization of some catalytic properties of liver mitochondrial and cytosolic NAD-dependent malate dehydrogenase (NAD-MDH; EC 1.1.1.37) from normal rats and rats with experimental toxic hepatitis (ETH) have been carried out. It has been found that there are some differences in catalytic and regulatory properties of liver NAD-MDH from control animals and rats with ETH. It has been shown that Fe2+ and Cu2+ ions inhibit the enzyme, and the inhibition degree is different at norm and under toxic hepatitis. Ca2+ ions insignificantly activate cytosolic NAD-MDH under pathology and do not influence the mitochondrial isoform.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Citoplasma/enzimología , Hígado/enzimología , Malato Deshidrogenasa/aislamiento & purificación , Mitocondrias Hepáticas/enzimología , Animales , Calcio/química , Catálisis , Cationes Bivalentes , Cobre/química , Activación Enzimática , Concentración de Iones de Hidrógeno , Hierro/química , Cinética , Malato Deshidrogenasa/antagonistas & inhibidores , Malato Deshidrogenasa/química , Masculino , Ácido Oxaloacético/química , RatasAsunto(s)
Virus de la Influenza A/genética , Virus de la Influenza A/metabolismo , ARN Viral/genética , ARN Viral/metabolismo , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/fisiología , Ensamble de Virus/fisiología , Secuencia de Aminoácidos , ADN/metabolismo , ADN Viral/metabolismo , Genes Virales , Genoma Viral , Leucina/química , Datos de Secuencia Molecular , Sistemas de Lectura Abierta , Filogenia , Homología de Secuencia de AminoácidoRESUMEN
NAD-dependent malate dehydrogenase activity decreased by 2.7 times in the myocardium of rats with experimental ischemia. Cytoplasmic NAD-dependent malate dehydrogenase from intact and ischemic rat heart was purified by 91.4 and 95.5 times. We compared kinetic characteristics and regulation of enzyme activity by Fe(2+), Cu(2+), Ca(2+), hydrogen peroxide, and glutathione under normal and pathological conditions.
Asunto(s)
Citoplasma/enzimología , Isquemia/metabolismo , Malato Deshidrogenasa/metabolismo , Miocardio/enzimología , Animales , Calcio/metabolismo , Cromatografía por Intercambio Iónico , Cobre/metabolismo , Electroforesis en Gel de Poliacrilamida , Glutatión/metabolismo , Peróxido de Hidrógeno/metabolismo , Hierro/metabolismo , Cinética , Malato Deshidrogenasa/aislamiento & purificación , Masculino , Ratas , Ratas MutantesRESUMEN
Experimental ishemia of rat myocardium was accompanied by increase of light sum (S) and maximal intensity (Imax) of chemiluminescence, amount of a malonic dialdehyde and conjugated dienes in cytoplasmic fraction. The activity of NADP-dependent malate dehydrogenase (EC 1.1.1.82; NADP-MDH) was 1.6 times higher in rat heart under ischemia. NADP-MDH was purified from normal and ischemia-exposed rat myocardium. Using NADP-MDH purified enzyme preparations the values of Hill coefficient for oxaloacetate (1.83 +/- 0.07 and 1.50 +/- 0.10) and Km for NADPH (0.058 +/- 0.003 and 0.096 +/- 0.004 mM) were determined for the enzyme at norm and under ischemia respectively. Effects of Fe2+, Ca2+, Cu2+ ions, H2O2, oxidized and reduced glutathione, adenine nucleotides influence on functioning of NADP-MDH from rat heart at norm and under ischemic conditions have been investigated.