RESUMO
The work was aimed to study relationship of monooxygenase system and lipid peroxidation in experiments and in clinical group. The examinees were workers engaged into graphite ware production and exposed to low fibrogenic dust of coke and graphite with carcinogens (including 3,4-benzpyrene). The experimental data and examination materials prove the carcinogens to alter seriously those systems. Long stimulation of monooxygenase system and activation of lipid peroxidation could result in more intensive carcinogenic effects of polycyclic aromatic hydrocarbons being a component of coal pitch.
Assuntos
Bronquite/etiologia , Carcinógenos/toxicidade , Coque/toxicidade , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Poeira/efeitos adversos , Grafite/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Doenças Profissionais/etiologia , Aminopirina N-Desmetilase/metabolismo , Anilina Hidroxilase/metabolismo , Animais , Benzo(a)pireno/toxicidade , Bronquite/induzido quimicamente , Sistema Enzimático do Citocromo P-450/metabolismo , Humanos , Técnicas In Vitro , Doenças Profissionais/induzido quimicamente , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Ratos , Ratos WistarRESUMO
The forms of catalase modified by treatment with dextran aldehyde were obtained and studied. Efficacy of the preparations containing native and modified forms of catalase and superoxide dismutase as well as their covalent bienzyme conjugate containing catalase-dextran aldehyde-superoxide dismutase was studied in rats with simulated silicosis. The preparations were administered into rats by means of inhalation and intraperitoneal injection. Positive protective effect exhibited a mixture of native enzymes and their covalent conjugate. The most pronounced additional effect was caused by the mixture of native catalase and superoxide dismutase as compared with modified preparation of superoxide dismutase. The preparation of bienzyme containing conjugate was less effective.
Assuntos
Catalase/uso terapêutico , Fibrose Pulmonar/tratamento farmacológico , Silicose/enzimologia , Superóxido Dismutase/uso terapêutico , Animais , Catalase/administração & dosagem , Catalase/química , Bovinos , Cromatografia em Gel , Dextranos/química , Fígado/enzimologia , Ratos , Superóxido Dismutase/administração & dosagem , Superóxido Dismutase/químicaRESUMO
Studies of monoxygenase system in rat liver exposed to tricresol showed, that the microsomal enzymes status depends on the route of tricresol administration and on the exposure intensity. Monoxygenase system status compared with the serum enzymes activity characterizing the function of the liver showed that changes in microsomal system are more marked, appear earlier and after lower levels of exposure. Changes of cytochrome P-450 enzyme system are the main principle of tricresol harmful action.
Assuntos
Cresóis/farmacologia , Hidrocarbonetos/farmacologia , Oxigenases/efeitos dos fármacos , Animais , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Sistema Enzimático do Citocromo P-450/metabolismo , Relação Dose-Resposta a Droga , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/enzimologia , Oxigenases/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The present paper dwells on biomedical study of aldehyde dextran modified superoxide dismutase. Pharmacokinetic data demonstrated that modification of superoxide dismutase increased its half-time. A rat model of experimental silicosis showed that aldehyde dextran modified superoxide dismutase inhibited evolving fibrosis in the lungs. The same dose of native enzyme produced no therapeutic effect. Thus, superoxide dismutase can be considered as a potential agent for treatment of fibrosis due to its modification.
Assuntos
Aldeídos/farmacologia , Dextranos/farmacologia , Fibrose Pulmonar/tratamento farmacológico , Silicose/tratamento farmacológico , Superóxido Dismutase/uso terapêutico , Animais , Meia-Vida , Masculino , Camundongos , Ratos , Ratos Endogâmicos , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
Investigation of protease inhibitors in the blood of silicosis and dust bronchitis patients revealed disbalance in the silicosis cases which manifested itself in growing elastase activity against normal protease inhibitors content--alpha 1 antitrypsin and alpha 2 macroglobuline. Meanwhile the silicosis cases, as compared with bronchitis, displayed greater biochemical changes, thus indicating inflammatory destructive processes in the lungs.
Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Bronquite/sangue , Elastase Pancreática/sangue , Quartzo/efeitos adversos , Dióxido de Silício/efeitos adversos , Silicose/sangue , alfa 1-Antitripsina/análise , alfa-Macroglobulinas/análise , Bronquite/etiologia , Poeira/efeitos adversos , Humanos , Silicose/etiologiaAssuntos
Bronquite/metabolismo , Carbono/efeitos adversos , Indústria Química , Grafite/efeitos adversos , Peroxidação de Lipídeos , Microssomos Hepáticos/metabolismo , Pneumoconiose/metabolismo , Adulto , Antioxidantes/metabolismo , Bronquite/etiologia , Poeira/efeitos adversos , Humanos , Pessoa de Meia-Idade , Pneumoconiose/etiologia , U.R.S.S.RESUMO
Content of lipid peroxides was increased in blood plasma of patients with dust-dependent diseases of lungs (fibrinogenous dust--pneumoconiosis, dust bronchitis; carcinogenous dust--dust bronchitis), whereas the tocopherol level was similar to normal values in pneumoconiosis and elevated in dust bronchitis. The increase in tocopherol content might be considered as a compensatory mechanism in response to augmented lipid peroxidation. At the same time, this compensation was not sufficiently effective, as a result of which the antioxidant activity was relatively decreased in blood plasma as well as the antioxidant control was impaired in tissues and accompanied by intensification of the free radical reactions.
Assuntos
Peróxidos Lipídicos/metabolismo , Pneumoconiose/metabolismo , Adulto , Bronquite/etiologia , Bronquite/metabolismo , Humanos , Pessoa de Meia-Idade , Silicose/etiologia , Silicose/metabolismo , Vitamina E/sangueRESUMO
Collagenase was gradually modified by aldehyde dextran and hyaluronidase. The modification increased enzyme stability and widened pH-optimum of its activity against specific and biological substrates. The modified complex with collagenolytic and hyaluronidase activity accumulated in the lungs of mice after intravenous injection. These results demonstrate its possible use for the treatment of lung disorders.
Assuntos
Colagenase Microbiana/farmacologia , Aldeídos/farmacocinética , Aldeídos/farmacologia , Animais , Catálise , Dextranos/farmacocinética , Dextranos/farmacologia , Hialuronoglucosaminidase/farmacocinética , Hialuronoglucosaminidase/farmacologia , Concentração de Íons de Hidrogênio , Masculino , Camundongos , Colagenase Microbiana/farmacocinética , Peso Molecular , Fatores de Tempo , Distribuição TecidualRESUMO
Dextran-modified hyaluronidase was inhaled or intraperitoneally injected for 4 months to mice with silicosis. Stabilized hyaluronidase was shown to have a marked inhibitory effect on the development of lung fibrosis. Drug inhalation proved to be the most effective. An antifibrotic effect of dextran itself has been observed.
Assuntos
Dextranos , Hialuronoglucosaminidase/uso terapêutico , Silicose/tratamento farmacológico , Administração por Inalação , Animais , Avaliação Pré-Clínica de Medicamentos , Estabilidade Enzimática/efeitos dos fármacos , Injeções Intraperitoneais , Pulmão/efeitos dos fármacos , Pulmão/patologia , Ratos , Ratos Endogâmicos , Silicose/patologiaRESUMO
Modified hyaluronidase derivatives have been obtained. Covalent coupling of the enzyme with aldehyde dextran results in 65-85% protein binding to the carrier, residual catalytic activity accounting for 90-100% of the baseline. Modified hyaluronidase is more thermostable than the native enzyme. The data on intravenous drug distribution in the mouse organs are promising and ensure effective use of modified hyaluronidase for the treatment of pulmonary diseases.
Assuntos
Dextranos , Hialuronoglucosaminidase , Animais , Hialuronoglucosaminidase/metabolismo , Técnicas In Vitro , Camundongos , Distribuição TecidualRESUMO
An increase in values of both kinetic parameters (Km and Vmax) of the delta-aminolevulinate dehydratase reaction was observed in blood of rats poisoned with lead. The Km value of the reaction was increased, while Vmax--decreased, after addition of Pb2+ into rat blood in vitro. The results obtained as well as the data published in literature suggest that a compensatory mechanism appears to function in vivo, where a substrate, delta-aminolevulenic acid, plays a triggering role.
Assuntos
Eritrócitos/enzimologia , Intoxicação por Chumbo/enzimologia , Sintase do Porfobilinogênio/sangue , Ácido Aminolevulínico/sangue , Animais , Catálise , Feminino , Cinética , Intoxicação por Chumbo/sangue , Sintase do Porfobilinogênio/antagonistas & inibidores , RatosRESUMO
Some theoretical and practical problems of controlling industrial environment and biological substrates in the CMEA countries are discussed. Particular attention has been paid to the unification of methodological instructions concerning common requirements and methods of supervision, as also to the coordination and unification of the methods of determining some chemical compounds in the air of the working zone and in biological materials.