RESUMO
The dynamics of radiation-induced oxidative and nitrative stress, the source of oxygen and nitrogen reactive species in cancer cell line K562 and the role of mitochondria in these processes have been studied. The study was performed using K562 leukemia cell cultures. Intracellular concentration of reactive oxygen species (ROS), nitrogen oxide, and the mitochondrial potential were analyzed after 15, 30 min, 1, 4, 8, 12, 24, and 48 h after irradiation by X-rays at a dose of 4 and 12 Gy. Radiation-induced generation of ROS in K562 cells has two time peaks, the first peak was recorded after 30 min and the second 24 h after exposure to X-rays. Mitochondria are responsible for the increase of the ROS concentration in the period of 12-48 h after irradiation. The increase in ROS concentrations is accompanied by the increase of the mitochondrial potential. The intracellular concentration of nitric oxide begins to grow 8 h after exposure. The increase in the mitochondria-dependent ROS production is accompanied by the increase in the intracellular concentration of nitric oxide.
Assuntos
Mitocôndrias/efeitos da radiação , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Raios X , Relação Dose-Resposta à Radiação , Humanos , Células K562 , Potencial da Membrana Mitocondrial/efeitos da radiação , Mitocôndrias/metabolismo , Óxido Nítrico/análise , Óxido Nítrico/biossíntese , Espécies Reativas de Nitrogênio/análise , Espécies Reativas de Oxigênio/análiseRESUMO
Results of a comparative study of the influence of doxorubicine (DOX) and dehydroepiandrosterone (DHEA) on cell proliferation and oxidative stress in Saccharomyces cerevisiae cells are presented. Three treatment schedules were assessed--DOX only, DHEA only, and DOX simultaneously with DHEA--in examining cell proliferation, measuring the content of glutathione, and evaluating the expression of ribonucleotide reductase in the test cells. The results indicate that the separate treatment with DOX or DHEA stimulates the expression of ribonucleotide reductase and leads to a decrease in the rate of cell proliferation. DHEA produces a dose-dependent decrease in the content of a reduced form of glutathione in cells, whereas the concentration of the oxidized form remains unchanged. In contrast, the treatment with DOX increased the concentrations of both forms of glutathione. The simultaneous treatment of cells by DOX and DHEA increased the accumulation of intracellular glutathione and decreased the total antiproliferative effect.
Assuntos
Adjuvantes Imunológicos/farmacologia , Antibióticos Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Doxorrubicina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Glutationa/metabolismo , Ribonucleotídeo Redutases/biossíntese , Proteínas de Saccharomyces cerevisiae/biossínteseRESUMO
The early nephrotoxicity manifestations (oxidative stress) caused by a single administration of doxorubicin in rats and the therapeutic effect of erythropoietin have been studied. The introduction of doxorubicin leads to a decrease in the concentration of glutathione and the activity of glutathione reductase in rat kidneys, which is indicative of the development of oxidative stress. Erythropoietin restores glutathione content on the normal level. The pretreatment with erythropoietin reduces the doxorubicin induced damage in rat kidneys.
Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/efeitos adversos , Eritropoetina/administração & dosagem , Rim/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Glutationa/metabolismo , Rim/lesões , Masculino , RatosRESUMO
The compound LKhT5391 (a derivative of nibentan) affects the electrophysiological cardiac parameters to a lower extent than does nibentan. Administered in an effective antiarrhythmogenic dose (comparable with the effective dose of nibentan), LKhT5391 produces a less pronounced and shorter negative chronotropic action than does nibentan. The negative dromotropic effect of the compound studied is manifested only in the atrioventricular node, while not influencing conductivity through the atria and ventricles.
Assuntos
Antiarrítmicos/farmacologia , Asparagina/análogos & derivados , Asparagina/farmacologia , Benzamidas/farmacologia , Coração/efeitos dos fármacos , Animais , Nó Atrioventricular/efeitos dos fármacos , Nó Atrioventricular/fisiologia , Gatos , Depressão Química , Feminino , Coração/fisiologia , Frequência Cardíaca/efeitos dos fármacos , MasculinoRESUMO
Experiments were conducted on models of early occlusion and reperfusion arrhythmias in cats to study the antiarrhythmic activity of trimecain, its morpholine analogue (MPT), and MPT derivatives containing glycine, magnesium salt of aspartic acid, and N-acetylglutaminic acid. All the compounds were injected in doses of 5% of LD50. A 22.5 mg/kg dose of trimecain prevented cardiac rhythm disorders after occlusion of the coronary arteries as well as after restoration of the coronary blood flow. Replacement of the diethyl group in the structure of trimecain by the morpholine ring led to diminution of antiarrhythmic activity, and MPT in a dose of 28.0 mg/kg, in distinction from the former, had no effect on the frequency of the occurrence of early occlusion arrhythmias and the duration of reperfusion arrhythmias. Introduction of amino acids as an anion into the MPT structure raised the antiarrhythmic activity of the last named.