RESUMO
Local effect of low-energy laser radiation was shown to alter the rate of lipid peroxidation in rat liver tissue which was manifested as a weak accumulation of primary and secondary lipid peroxidation products. The laser radiation effect proved to be generalized as the content of lipid peroxidation products was similarly altered both in liver tissue and in blood regardless of the radiation site.
Assuntos
Lasers , Peroxidação de Lipídeos/efeitos da radiação , Animais , Eritrócitos/metabolismo , Eritrócitos/efeitos da radiação , Fígado/metabolismo , Fígado/efeitos da radiação , Malondialdeído/sangue , Malondialdeído/metabolismo , Ratos , Superóxido Dismutase/metabolismoRESUMO
The effect of chronic administration of 0.002% N-nitrosodiethylamine (DENA), 0.002% diethylamine (DEA) and 0.0005% sodium nitrite (SN) on the functional state of the xenobiotic metabolizing system in rat liver was investigated. Administration of DEA and DENA increased concentration of cytochromes P-450 and b5. SN did not affect the enzymes of the monooxygenase system. Coadministration of DEA and SN maximally increased the concentration of cytochrome P-450. It is not possible to explain the phenomenon of combined administration of SN and DEA by simple summation of the effects caused by them separately. The activity of microsomal glutathione S-transferase did not change when DEA and SN were given together, yet increased when they were administered separately. The maximum increase of the total activity of cytosol glutathione S-transferases was observed following DENA. In all four experimental groups a decrease of isoenzyme 5-5 activity was observed. Investigation of Se-independent glutathione peroxidase activity showed the multivariance of response of the glutathione S-transferase family to the compounds studied. The concentration of hepatic free SH-groups increased following administration of DENA and decreased dramatically when SN and DEA were coadministered. When they were given separately the concentration remained at control level.
Assuntos
Alquilantes/farmacologia , Dietilnitrosamina/farmacologia , Fígado/metabolismo , Xenobióticos/metabolismo , Animais , Sistema Enzimático do Citocromo P-450/metabolismo , Citosol/efeitos dos fármacos , Citosol/enzimologia , Citosol/metabolismo , Dietilaminas/farmacologia , Glutationa Transferase/metabolismo , Técnicas In Vitro , Fígado/enzimologia , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Ratos , Nitrito de Sódio/farmacologiaRESUMO
The state of the xenobiotic biotransformation system has been studied after a single per os administration of diphenylamine (DPA) and N-nitrosodiphenylamine (NDPA) to male albino rats. Intoxication of animals with NDPA induced unidirectional and similar changes in the functional states of the both stages of the xenobiotic metabolism. There was an increase in the total content of cytochrome P-450 and the activity of NADPH-cytochrome P-450 reductase as well as a marked elevation of activity of microsomal glutathione S-transferase. This was paralleled with the induction of activity of individual isoenzymes of the multifunctional family of rat liver cytosol glutathione S-transferases and increased activity of glutathione reductase. Unlike NDPA, DPA affected only the second stage of the xenobiotic biotransformation by stimulating the activity of both membrane-bound and soluble glutathione S-transferases. In both cases the intoxication was attended by an increase in the number of SH-groups unbound to the protein. It was assumed that the different response of the xenobiotic biotransformation system to DPA and NDPA may be due to the appearance of a N-nitroso group in the NDPA molecule.
Assuntos
Difenilamina/toxicidade , Nitrosaminas/toxicidade , Xenobióticos/toxicidade , Animais , Biotransformação , Difenilamina/farmacocinética , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Fígado/enzimologia , Masculino , Nitrosaminas/farmacocinética , Ratos , Xenobióticos/farmacocinéticaRESUMO
It has been shown that benzidine administered in vivo attenuates the protective effect of the antioxidant system manifested as a reduction of the total antioxidant activity of rat liver cytosol and decreasing activities of superoxide dismutase and catalase. Enomelanin promotes the reconstitution of the superoxide dismutase activity. The data obtained suggest that the toxic effect of benzidine may be due to disturbances in the antioxidant protective mechanisms of liver cells responsible for the control over the free radical processes occurring in those cells.
Assuntos
Antioxidantes/metabolismo , Benzidinas/intoxicação , Fígado/enzimologia , Melaninas/uso terapêutico , Animais , Catalase/metabolismo , Radicais Livres , Masculino , Melaninas/administração & dosagem , Intoxicação/tratamento farmacológico , Ratos , Superóxido Dismutase/metabolismoAssuntos
Glutamatos/metabolismo , Glutamatos/efeitos da radiação , Lasers , Animais , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/efeitos da radiação , Encéfalo/enzimologia , Encéfalo/efeitos da radiação , Citoplasma/enzimologia , Citoplasma/efeitos da radiação , Feminino , Glutamato Desidrogenase/metabolismo , Glutamato Desidrogenase/efeitos da radiação , Ácido Glutâmico , Isoenzimas/metabolismo , Isoenzimas/efeitos da radiação , Mitocôndrias/enzimologia , Mitocôndrias/efeitos da radiação , Mitocôndrias Hepáticas/enzimologia , Mitocôndrias Hepáticas/efeitos da radiação , Ratos , Irradiação Corporal Total , Raios XRESUMO
The effects of diaminobiphenyl, biphenylamine and tetraaminobiphenyl on lipid peroxidation and antioxidant protective mechanisms in the subcellular fractions of rat liver have been studied. It was found that activation of lipid peroxidation plays a crucial role in the manifestation of hepatotoxic activities of diaminobiphenyl and biphenylamine, this effect being due to the decrease of the protective activity of the antioxidant system during intoxication by these compounds. Tetraaminobiphenyl does not influence the rate of lipid peroxidation. It is concluded that structural differences determine the differences in the mechanisms of adaptation of the antioxidant system to the effect of aromatic amines.
Assuntos
Compostos de Aminobifenil/toxicidade , Antioxidantes/metabolismo , Fígado/efeitos dos fármacos , Compostos de Aminobifenil/metabolismo , Animais , Radicais Livres , Peroxidação de Lipídeos , Fígado/enzimologia , Fígado/metabolismo , Masculino , RatosRESUMO
Actin was purified from rat sarcoma-45 by using affinity chromatography on DNase I agarose. Actin was detected in the soluble and cytoskeletal fractions. The molecular mass of the protein was found to be equal to 45 kDa. The tumour actin specifically reacted with the antibody against skeletal muscle actin, inhibited the DNAase I activity and activated in the fibrillar state Mg(2+)-ATPases of sarcoma-45 and skeletal muscle myosins. The activating effect of the tumour protein was lower than that of its skeletal muscle counterpart. V8-protease peptide mapping revealed a similarity between tumour and brain actins. Sarcoma-45 actin was found to contain beta- and gamma-actin isoforms and an unusual isoform which appeared to be more acidic than the alpha-actin isoform.
Assuntos
Actinas/metabolismo , Sarcoma Experimental/metabolismo , Actinas/isolamento & purificação , Animais , ATPase de Ca(2+) e Mg(2+)/metabolismo , Desoxirribonuclease I/metabolismo , Eletroforese em Gel Bidimensional , Eletroforese em Gel de Poliacrilamida , Miosinas/metabolismo , Pâncreas/enzimologia , RatosRESUMO
A number of metabolic parametres were studied in subcellular fractions of rat sarcoma 45, M-1 and carcinosarcoma Worker 256. Administration of high doses of glucose amplified some effects of chemotherapeutic drugs and X-ray therapy, which were manifested as follows: a decrease in glycolysis rate, alteration in the rate of redox reactions, shifts in the ratio between glycolysis and biological oxidation in mitochondria. These alterations were determined by the type of sarcoma, by sequence of operations in the procedure and by cytostatic used. The most effective procedure proved to be simultaneous administration of drugs and X-ray therapy followed by hyperglycemia. Distinct inhibition of glycolysis defected under these conditions may contribute to inhibition of energy metabolism during the sarcoma growth and regression.
Assuntos
Carcinoma 256 de Walker/terapia , Hiperglicemia , Sarcoma Experimental/terapia , Aminoácidos/metabolismo , Animais , Metabolismo dos Carboidratos , Carcinoma 256 de Walker/tratamento farmacológico , Carcinoma 256 de Walker/metabolismo , Carcinoma 256 de Walker/radioterapia , Terapia Combinada , Metabolismo Energético , Feminino , Glicólise , Masculino , Ratos , Sarcoma Experimental/tratamento farmacológico , Sarcoma Experimental/metabolismo , Sarcoma Experimental/radioterapiaRESUMO
It was found that intoxication of animals with aminobiphenyls leads to the activation of such glutathione-dependent enzymes as glutathione-S-transferase and glutathione reductase. This is accompanied by the induction of activities of individual isoforms of the multifunctional family of glutathione-S-transferases. There was a decrease in the glutathione peroxidase activity after intoxication with benzidine derivatives. It was found that the GSH content in rat liver decreased after benzidine intoxication and sharply increased after effects of 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine. In all cases studied there was a diminution in the level of diene conjugates. It was supposed that the specificity of the catalytic glutathione redox system reaction is due to structural peculiarities of the aminobiphenyls being injected. Analysis of functional pairs of glutathione-dependent enzymes revealed a certain imbalance in the antioxidant system function after aminobiphenyl poisoning.
Assuntos
Compostos de Aminobifenil/intoxicação , Antioxidantes , Benzidinas , Carcinógenos , Peroxidação de Lipídeos , Fígado/metabolismo , Animais , Dianisidina/intoxicação , Glutationa Redutase/metabolismo , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Oxirredução , RatosAssuntos
Córtex Cerebral/efeitos da radiação , Lasers , ATPase Trocadora de Sódio-Potássio/efeitos da radiação , Sinaptossomos/efeitos da radiação , Trifosfato de Adenosina/metabolismo , Animais , ATPase de Ca(2+) e Mg(2+)/metabolismo , ATPase de Ca(2+) e Mg(2+)/efeitos da radiação , Córtex Cerebral/enzimologia , Hidrólise , Masculino , Ratos , ATPase Trocadora de Sódio-Potássio/metabolismo , Sinaptossomos/enzimologia , Fatores de TempoRESUMO
Modification of histidine residues, SH- and epsilon-NH2-groups of myosin from rat sarcoma-45 by specific reagents was studied. It was shown that diethylpyrocarbonate modifies histidine residues essential for the ATPase activity. A kinetic analysis of myosin epsilon-NH2-groups modification by 2,4,6-trinitrobenzene sulfonate revealed that myosin trinitrophenylation and its inactivation by Ca2(+)-ATPase occurs in two steps: a fast and a slow (Km = 2400 and 1.7 s-1 M-1, respectively). Two essential epsilon-NH2-groups of tumour myosin active sites react in the fast reaction. The relatively low concentrations of p-chloromercuribenzoic acid activate rat sarcoma-45 myosin Ca2(+)-ATPase and Mg2(+)-ATPase, whereas higher ones inhibit the enzyme. The data obtained suggest that two SH-groups, SH1 and SH2 are essential for the tumour myosin ATPase function.
Assuntos
Cloromercurobenzoatos/farmacologia , Dietil Pirocarbonato/farmacologia , Miosinas/efeitos dos fármacos , Proteínas de Neoplasias/efeitos dos fármacos , Sarcoma Experimental/química , Ácido Trinitrobenzenossulfônico/farmacologia , Aminas/química , Animais , ATPase de Ca(2+) e Mg(2+)/efeitos dos fármacos , ATPases Transportadoras de Cálcio/efeitos dos fármacos , Histidina/efeitos dos fármacos , Ratos , Reagentes de Sulfidrila , Ácido p-CloromercurobenzoicoRESUMO
Myosin was purified from rat tumour sarcoma-45 whose properties (effects of cations on ATPase activity, substrate specificity, temperature- and pH-optima, thermal stability, sensitivity of Mg2(+)-ATPase to F-actin, molecular mass, subunit composition) are similar to those of fast skeletal muscle myosin. Some parameters of the protein, namely, the levels of Ca2(+)- and K+, EDTA-ATPase activity, relative content of myosin light chains with Mr 16500 and the degree of tumoural myosin Mg2(+)-ATPase activation by F-actin, were significantly lower than those of skeletal muscle myosin.
Assuntos
Miosinas/isolamento & purificação , Sarcoma Experimental/análise , Actinas/análise , Adenosina Trifosfatases/análise , Animais , Cromatografia em Gel , Concentração de Íons de Hidrogênio , Peso Molecular , Miosinas/análise , Ratos , Sarcoma Experimental/enzimologia , Especificidade por SubstratoRESUMO
In experiments in vivo it was shown that upon low-intensity infrared irradiation changes in the activity of main enzymes of glutamic acid metabolism are a function of time of exposure and flux density.
Assuntos
Aspartato Aminotransferases/efeitos da radiação , Encéfalo/efeitos da radiação , Glutamato Desidrogenase/efeitos da radiação , Raios Infravermelhos , Lasers , Animais , Aspartato Aminotransferases/metabolismo , Encéfalo/enzimologia , Glutamato Desidrogenase/metabolismo , Isoenzimas/metabolismo , Isoenzimas/efeitos da radiação , Fosfato de Piridoxal/metabolismo , Fosfato de Piridoxal/efeitos da radiação , Piridoxamina/análogos & derivados , Piridoxamina/metabolismo , Piridoxamina/efeitos da radiação , Ratos , Fatores de TempoRESUMO
Kinetic parameters of the inhibitory effect of vincristine on Mg2+ATPase activity containing in the actomyosin-like protein from rat sarcoma 45 and in actomyosin from rat skeletal muscle was studied. The alkaloid decreased the VM value for the reaction catalyzed by ATPase in presence of Mg2+ and EGTA and did not alter Km value for both contractile proteins. Inhibitory constants, calculated for the actomyosin from skeletal muscles and for the actomyosin-like protein from sarcoma 45, constituted 520 mcM and 250 mcM, respectively. Vincristine appears to inhibit Mg2+-ATPase containing in these contractile proteins studied by the non-competitive type, simultaneously with lowering of the activating effect of actin on the myosin-derived ATPase.
Assuntos
Actomiosina/metabolismo , ATPase de Ca(2+) e Mg(2+)/antagonistas & inibidores , Músculos/enzimologia , Sarcoma Experimental/enzimologia , Vincristina/farmacologia , Animais , Ácido Egtázico , Cinética , Magnésio/farmacologia , Ratos , Sarcoma Experimental/metabolismoRESUMO
A study was made of the effect of a single exposure of rats to 0.4 Gy X-radiation on the content of pyridoxal phosphate and pyridoxamine phosphate in gray and white brain substances and liver. At the same time changes were noted in the activity of pyridoxal kinase in the tissues under study.
Assuntos
Encéfalo/efeitos da radiação , Coenzimas/metabolismo , Fígado/efeitos da radiação , Fosfato de Piridoxal/metabolismo , Piridoxamina/análogos & derivados , Animais , Encéfalo/enzimologia , Fígado/enzimologia , Masculino , Piridoxal Quinase/metabolismo , Piridoxamina/metabolismo , RatosRESUMO
Activity of hexokinase and acetylcholinesterase and pyridoxal co-enzyme content of brain subcellular fractions were studied in rats, bearing sarcoma 45, after local exposure of the tumor to 20 Gy X-radiation and microwave hyperthermia. The carbohydrate metabolism was sharply inhibited while the pyridoxal coenzyme content and acetylcholinesterase activity increased.
Assuntos
Encéfalo/enzimologia , Hipertermia Induzida , Sarcoma Experimental/enzimologia , Acetilcolinesterase/metabolismo , Acetilcolinesterase/efeitos da radiação , Animais , Encéfalo/efeitos da radiação , Hexoquinase/metabolismo , Hexoquinase/efeitos da radiação , Masculino , Transplante de Neoplasias , Fosfato de Piridoxal/metabolismo , Fosfato de Piridoxal/efeitos da radiação , Piridoxamina/análogos & derivados , Piridoxamina/metabolismo , Piridoxamina/efeitos da radiação , Ratos , Ratos Endogâmicos , Sarcoma Experimental/radioterapia , Fatores de TempoRESUMO
In the in vivo experiments it has been shown that a mixture of low-intensity helium-neon laser radiation and dyes modifies the effect of laser radiation on the activity of basic enzymes of glutamic acid metabolism.
Assuntos
Encéfalo/efeitos da radiação , Corantes/farmacologia , Glutamatos/metabolismo , Lasers , Animais , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/efeitos da radiação , Encéfalo/enzimologia , Glutamato Desidrogenase/metabolismo , Glutamato Desidrogenase/efeitos da radiação , Ácido Glutâmico , Isoenzimas/metabolismo , Isoenzimas/efeitos da radiação , Terapia a Laser , Fígado/enzimologia , Masculino , Fotoquimioterapia , RatosRESUMO
Chronic gamma-irradiation during 3.5 and 6 months (at a dose = rate of 46.2 pC/kg X c) of Microtus oeconomus living in conditions of normal and increased (by 50-100 times) gamma-radiation background, and of their progeny (the 1st, 2nd, 3d, and 4th generations) causes in homogenates of cardiac muscle, liver, and brain different changes in activity of succinate dehydrogenase (1.3.99.1, EC), pyruvate dehydrogenase (1.2.4.1, EC), and lactate dehydrogenase (1.1.1.27, EC) associated with the discordance of the processes of tissue respiration and glycolysis. The changes in dehydrogenases activity in Microtus oeconomus subjected to chronic irradiation were nearly the same as those found in their parents.