RESUMO
The dynamics of total protein biosynthesis and procollagen biosynthesis in skeletal muscle of injury tissues with the antioxidant BHT (dibunol) treatment and with common healing were studied. The obtained date indicate that the AO treatment reduce the rate of biosynthesis both the total proteins and procollagen at the 3th day of healing. Dibunol also considerably reduce the protein biosynthesis in adrenals and brake of corticosteroids biogenesis as measured by ESR-signals intensity of reduced adrenodoxine. AO treatment also reduce the protein biosynthesis in thymus, spleen and bone marrow. The lowering of functional activity of endocrine and immune systems indicate that the AO significantly inhibit the systemic reactions of organism induced by acute wound affect. It was suggested that as "primary mediator" of stress-reaction may be considered lipoperoxide radicals and decay products of lipohydroperoide.
Assuntos
Antioxidantes/farmacologia , Hidroxitolueno Butilado/farmacologia , Síndrome de Adaptação Geral/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Ferimentos por Arma de Fogo/metabolismo , Animais , Sistema Endócrino/efeitos dos fármacos , Sistema Endócrino/metabolismo , Radicais Livres/metabolismo , Síndrome de Adaptação Geral/tratamento farmacológico , Sistema Imunitário/efeitos dos fármacos , Sistema Imunitário/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Ratos , Ratos Wistar , Cicatrização/efeitos dos fármacos , Ferimentos por Arma de Fogo/tratamento farmacológicoAssuntos
Antioxidantes/uso terapêutico , Barotrauma/metabolismo , Barotrauma/prevenção & controle , Ferro/metabolismo , Óxidos de Nitrogênio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Vísceras/lesões , Animais , Antioxidantes/administração & dosagem , Óxidos N-Cíclicos/administração & dosagem , Radicais Livres/metabolismo , Ferro/análise , Fígado/química , Fígado/metabolismo , Óxidos de Nitrogênio/análise , Coelhos , Ratos , Ratos Wistar , Marcadores de Spin , Vísceras/efeitos dos fármacosRESUMO
The decrease of sorbitol dehyidrogenase activity and the increase both of aldoso reductase activity and sorbitol concentration in aorta or eye lens under experimental diabetic angiopathy have been shown. The structural and functional alterations in erythrocytes membranes under angiopathy studied by spin- and luminesoense probes confirm the hypothesis on the major role of membrane pathology processes in the pathogenesis of diabetic mellitus. Pharmacological correction of diabetic angiopathy by glucophag or new antioxidant LBK-78 normalized the studied diversions on the membranes level.
Assuntos
Antioxidantes/uso terapêutico , Angiopatias Diabéticas/metabolismo , Membrana Eritrocítica/metabolismo , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Compostos Orgânicos , Animais , Angiopatias Diabéticas/tratamento farmacológico , Membrana Eritrocítica/efeitos dos fármacos , Masculino , Ratos , Sorbitol/metabolismoRESUMO
Both intact mice and those with transplantable adenocarcinoma 755 were used in the investigation. The nitroxyl radical Tempol was shown to cut down the toxicity of 6-mercaptopurine and potentiate its antitumor effect to a certain degree. The study results suggest on the basis of an investigation of cytochrome P450 and some other evidence that said effect of Tempol might be due, at least, in part to antioxidant activity.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/toxicidade , Antimetabólitos Antineoplásicos/uso terapêutico , Antineoplásicos/antagonistas & inibidores , Antioxidantes/farmacologia , Óxidos N-Cíclicos/farmacologia , Mercaptopurina/antagonistas & inibidores , Mercaptopurina/uso terapêutico , Animais , Antineoplásicos/toxicidade , Relação Dose-Resposta a Droga , Esquema de Medicação , Sinergismo Farmacológico , Masculino , Mercaptopurina/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Marcadores de Spin , Análise de SobrevidaRESUMO
Low selectivity of contemporary antitumor drugs requires a search for its improvement. In this context, nitroxyl radicals are of interest as promising pharmacological agents. The introduction of nitroxyl radical into the structure of antitumor cytostatics was found to reduce considerably their general and specific toxicity. In this work, we demonstrate a detoxifying effect of tempol upon its combined injection with cytostatics at their absolute lethal dose in the intact mice as well as an improvement of sensitivity of tumor-bearing animals to 6-MP. Tempol is shown to normalize the level of oxidized form of P450 cytochrome in a liver, reduced as a result of the injection of 6-MP.
Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Óxidos N-Cíclicos/farmacologia , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Fígado/efeitos dos fármacos , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/enzimologia , Mercaptopurina/farmacologia , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Sinergismo Farmacológico , Feminino , Fígado/enzimologia , Camundongos , Camundongos Endogâmicos C57BL , Marcadores de SpinRESUMO
Nitroxyl radicals of a series of piperidineoxyles and pirrolinoxyles increase the tolerance of experimental animals to the injection of otherwise lethal doses of anti-tumor cytostatic agents. Simultaneous injection of nitroxyl radicals in different doses with 6-mercaptopurine, thiophosphamide, cyclophosphamide and the other cytostatic agents results in decreased toxicity and survival of animals. Nitroxyl radicals normalize the level of the oxidized form of P450 cytochrome that is decreased by the injection of lethal doses of cytostatic agents.
Assuntos
Antineoplásicos/toxicidade , Óxidos de Nitrogênio/farmacologia , Animais , Ciclofosfamida/farmacologia , Ciclofosfamida/toxicidade , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/fisiologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Radicais Livres/farmacologia , Mercaptopurina/farmacologia , Mercaptopurina/toxicidade , Camundongos , Tiotepa/farmacologia , Tiotepa/toxicidadeRESUMO
Pharmacokinetics of a spin-labeled analog of rubomycin (ruboxyl) was studied. Differences were found in ruboxyl pharmacokinetics in normal and tumor-bearing animals. Most of the drug was excreted within 6 h. The differences in pharmacokinetics of ruboxyl and nitroxyl radical were established.
Assuntos
Daunorrubicina/análogos & derivados , Sarcoma 180/metabolismo , Animais , Daunorrubicina/farmacocinética , Daunorrubicina/uso terapêutico , Espectroscopia de Ressonância de Spin Eletrônica , Fígado/metabolismo , Camundongos , Sarcoma 180/tratamento farmacológico , Distribuição TecidualRESUMO
ESR study was carried out of the content of oxidized form of cytochrom P-450 at regenerative processes in the liver. It has been shown that after partial hepatectomia and the effect of cycloheximid in the liver of experimental animals regular gradual changes of the content of the paramagnetic form of cytochrom P-450 are observed, an inverse correlation between these changes and protein biosynthesis being noted.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Ferro/metabolismo , Regeneração Hepática , Fígado/metabolismo , Animais , Cicloeximida/farmacologia , Espectroscopia de Ressonância de Spin Eletrônica , Fígado/efeitos dos fármacos , Oxirredução , Biossíntese de Proteínas/efeitos dos fármacos , Ratos , Ratos EndogâmicosAssuntos
Leucemia Experimental/metabolismo , Fígado/metabolismo , Animais , Compostos Azo/uso terapêutico , Radicais Livres , Hidroxiquinolinas/uso terapêutico , Leucemia L1210/metabolismo , Leucemia Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos AKR , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Transplante de Neoplasias , Especificidade da Espécie , Succinatos/uso terapêuticoRESUMO
Paramagnetic properties of frozen samples of normal, fetal and regenerating liver tissues and of a number transplantable hepatomas of different level of differentiation were studied. The results obtained indicate that ESR spectrum character and the concentration of paramagnetic centres in frozen samples of live tissues as well reflect the differentiation level, and the level of tissue functional activity. It is shown of hepatoma 22 taken as an example that tumour growth is accompanied with a change of the content of free radicals and some paramagnetic centres in the tumour and hosts liver. It can be considered as a manifestation of a biophysical shift which characterizes the tumour growth and includes the system effect of the tumour on the organism.