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1.
Biokhimiia ; 54(11): 1847-51, 1989 Nov.
Artigo em Russo | MEDLINE | ID: mdl-2483347

RESUMO

The effect of the membranotropic agent alkylresorcinol 5C10 on the respiration, nucleic acid and protein synthesis in isolated thymocytes was studied. Within the 5C10 concentration range of 10(-7)-10(-5) M, the inhibition of respiration and incorporation of labelled precursors into thymocyte proteins and DNA was observed. In case of respiration and protein synthesis, a 50% inhibition was observed at alkylresorcinol concentrations of 10(-8) and 0.5.10(-5) M, respectively. The rate of 3H-thymidine incorporation into DNA progressively decreased already at 5C10 concentration of 10(-7) M. At 10(-6) M alkylresorcinol its inhibiting effect on DNA synthesis was about 30% and it did not change with a further rise in the inhibitor concentration up to 10(-5) M. In contrast, the rate of RNA synthesis significantly increased (ca. by 20%) within the alkylresorcinol concentration range of 10(-6)-10(-5) M. At 5C10 concentrations above 10(-5) M, the state of thymocytes in the preagglutination period appeared to be critical and was characterized by a dramatic inhibition of all the parameters under study. The experimental results suggest that alkylresorcinol 5C10 causes the inhibition of processes that are functionally coupled with biological membranes.


Assuntos
DNA/biossíntese , Consumo de Oxigênio/efeitos dos fármacos , Biossíntese de Proteínas , RNA/biossíntese , Resorcinóis/farmacologia , Timo/metabolismo , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Inibidores da Síntese de Proteínas , Ratos , Ratos Endogâmicos , Timo/citologia , Timo/efeitos dos fármacos
2.
Biokhimiia ; 54(9): 1440-4, 1989 Sep.
Artigo em Russo | MEDLINE | ID: mdl-2590683

RESUMO

It was shown that during glutamate+malate oxidation in the presence of creatine, antitumour anthracycline antibiotics strongly inhibit the rate of oxygen uptake by rat heart mitochondria; ADP excess activated the respiration up to the initial level, i.e., that observed after the first addition of ADP. Carboxyatractyloside addition to a system containing creatine (or hexokinase+glucose) results in the stimulation of rubomycin-induced mitochondrial respiration. Substitution of carboxyatractyloside by oligomycin gives very similar results. It is supposed that anthracycline antibiotics exert a manyfold effect on heart mitochondrial membranes which results in impaired compartmentation of enzymatic systems providing for oxidative phosphorylation.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Creatina Quinase/metabolismo , Mitocôndrias Cardíacas/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Difosfato de Adenosina/metabolismo , Animais , Atractilosídeo/análogos & derivados , Atractilosídeo/farmacologia , Daunorrubicina/farmacologia , Interações Medicamentosas , Oxirredução , Ratos
3.
Antibiot Khimioter ; 34(8): 589-93, 1989 Aug.
Artigo em Russo | MEDLINE | ID: mdl-2480083

RESUMO

The effect of anthracycline antibiotics such as carminomycin, daunomycin (rubomycin) and adriamycin on respiration and synthesis of nucleic acids and protein was studied comparatively. The anthracyclines inhibited the processes. By their efficacy in that respect they could be arranged in the following order: carminomycin greater than rubomycin greater than adriamycin. Thus, 50 per cent inhibition of nucleic acid synthesis in the thymocytes required 0.027, 0.044 and 0,173 mM of carminomycin, rubomycin and adriamycin respectively. Protein synthesis and respiration in the thymocytes were less sensitive to the effect of the anthracyclines than synthesis of nucleic acids. The study results were compared with the literature data on the effect of the compounds on respiration and synthesis of nucleic acids and protein in tumour and bacterial cells.


Assuntos
Antibióticos Antineoplásicos/farmacologia , DNA/biossíntese , Linfócitos/metabolismo , Nucleoproteínas/biossíntese , Consumo de Oxigênio/efeitos dos fármacos , RNA/biossíntese , Timo/citologia , Animais , DNA/antagonistas & inibidores , DNA/efeitos dos fármacos , Depressão Química , Técnicas In Vitro , Linfócitos/efeitos dos fármacos , Nucleoproteínas/antagonistas & inibidores , RNA/antagonistas & inibidores , RNA/efeitos dos fármacos , Ratos , Ratos Endogâmicos
4.
Biokhimiia ; 53(2): 227-32, 1988 Feb.
Artigo em Russo | MEDLINE | ID: mdl-3163503

RESUMO

The anthracycline antibiotics rubomycin (daunorubicin) and carminomycin at concentrations which stimulate mitochondrial respiration in the absence of ADP induce the swelling of rat liver mitochondria. Under these conditions, the lipid peroxidation (LPO) inhibitor ionol slows down both the respiration and swelling of mitochondria. This suggests that stimulation of respiration and swelling under effects of the antibiotics largely depend on LPO. In the presence of the respiration inhibitor antimycin no effect of ionol is observed. Adriamycin (doxorubicin) stimulates mitochondrial respiration in a lesser degree than rubomycin and carminomycin and fails to induce mitochondrial swelling.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Mitocôndrias Hepáticas/efeitos dos fármacos , Dilatação Mitocondrial/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Animais , Hidroxitolueno Butilado/farmacologia , Carrubicina/farmacologia , Daunorrubicina/farmacologia , Doxorrubicina/farmacologia , Técnicas In Vitro , Membranas Intracelulares/efeitos dos fármacos , Membranas Intracelulares/metabolismo , Peróxidos Lipídicos/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Naftacenos/farmacologia , Permeabilidade , Ratos
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