RESUMO
The protective effect of three dithiocarbamates against lung tissue damage induced by a single intratracheal instillation of cadmium chloride was examined in rats. The relative efficacy of these compounds was tested by comparing characteristic features of lung tissue damage: the increase of lung weight, and the changes in the synthesis and content of structural proteins. Of three compounds administered intraperitoneally at a dose of 2.46 mmol/kg body weight, the most effective in suppressing lung damage was sodium bis(hydroxyethyl)dithiocarbamate (DEDTC). Its efficacy was dependent on the time interval between administration of cadmium chloride and the DEDTC. The parameters of lung tissue damage which were examined approached control values when DEDTC and cadmium chloride were administered simultaneously.
Assuntos
Intoxicação por Cádmio/prevenção & controle , Cádmio/antagonistas & inibidores , Ditiocarb/uso terapêutico , Pneumopatias/induzido quimicamente , Animais , Cádmio/metabolismo , Intoxicação por Cádmio/patologia , Tecido Conjuntivo/efeitos dos fármacos , Tecido Conjuntivo/metabolismo , Cobre/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Pneumopatias/patologia , Pneumopatias/prevenção & controle , Masculino , Tamanho do Órgão/efeitos dos fármacos , Piperidinas/uso terapêutico , Intoxicação/tratamento farmacológico , Ratos , Ratos Endogâmicos , Sorbitol/análogos & derivados , Sorbitol/uso terapêutico , Tiocarbamatos/uso terapêutico , Zinco/metabolismoRESUMO
Changes of soluble and insoluble fractions of pulmonary connective tissue proteins were studied in rats for 2-84 days following a single intratracheal instillation of cadmium chloride (10 micrograms Cd2+/lung). A transient decrease in body weight and an immediate increase in lung wet weight (200% of control value, P less than 0.01) were observed. Incorporation of [14C]proline and its conversion to [14C]hydroxyproline in vivo into different soluble and insoluble fractions of connective tissue revealed an increased metabolic turnover elicited by cadmium intoxication. A lag in the maturation of collagen into higher functional forms in the early phase of the process was demonstrated. A striking decrease in elastin was found in first 7 days (40-50%). However, this acute damage of pulmonary connective tissue was followed by a permanent increase of collagen and elastin concentration in the later phase of recovery. Histopathologic examination 14-84 days after cadmium instillation confirmed the presence of lesions in pulmonary tissue with an initial inflammation followed by reparatory changes.
Assuntos
Cádmio/toxicidade , Colágeno/metabolismo , Tecido Conjuntivo/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Cloreto de Cádmio , Radioisótopos de Carbono , Colágeno/biossíntese , Tecido Conjuntivo/metabolismo , Elastina/metabolismo , Hidroxiprolina/análise , Pulmão/patologia , Masculino , Prolina/metabolismo , Ratos , Ratos EndogâmicosRESUMO
The effect of a single intratracheal instillation of 2 mg of papain on metabolic changes of collagen and elastin in lungs was studied in rats labeled with [14C]proline in vivo. The total amount, concentration, specific and total radioactivity of both proteins were examined during the 28 days after papain administration. In the early period (1 to 3 days) a loss of elastin content (about 50% of control; p less than 0.01) was found, whereas collagen content increased (p less than 0.05). Simultaneously, the specific as well as the total radioactivity of both proteins was enhanced (p less than 0.01) which indicated an accelerated biosynthesis and metabolic turnover. This fact was reflected in the increased amounts of both collagen and elastin in the lungs 14 and 28 days after instillation of the enzyme. The changes in connective tissue proteins accompanied a large increase in lung weight (200% that of the control rats; p less than 0.01) immediately after the exposure. Toward the end of the 28-day period, the increase was smaller. The enzymatic damage probably induced the formation of nonfunctional elastin and fibrous scars as a consequence of the healing process.