RESUMO
Methylmercury was given to 30-day-old Wistar rats, At 1-7 days later the protein and RNA synthesis was studied in vivo by injecting a mixture [14C]leucine and [3H]uridine. Protein and RNA were precipitated from isolated cerebral and cerebellar neurons. The reduction of RNA synthesis coincides or precedes the reduced protein synthesis.
Assuntos
Encéfalo/efeitos dos fármacos , Compostos de Metilmercúrio/toxicidade , Proteínas do Tecido Nervoso/biossíntese , RNA/biossíntese , Animais , Encéfalo/metabolismo , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos , Ratos EndogâmicosRESUMO
Uptake of mercury by brain after i.v. injection of elemental mercury was investigated in the rat, after depletion of glutathione or inhibition of glutathione peroxidase in brain tissue. When glutathione in brain was depleted 76% by an intraventricular injection of diethylmaleate, a 13% increase in mercury uptake by brain was observed. After an intraventricular injection of iodoacetate, activity of glutathione peroxidase in brain was inhibited 19% and the content of reduced glutathione was decreased 20%. In these animals mercury uptake by brain increased 66% relative to controls.
Assuntos
Encéfalo/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa/metabolismo , Mercúrio/metabolismo , Animais , Transporte Biológico , Encéfalo/efeitos dos fármacos , Iodoacetatos/farmacologia , Ácido Iodoacético , Cinética , Masculino , Maleatos/farmacologia , Ratos , Ratos EndogâmicosRESUMO
Autopsy specimens of liver and kidneys from 40 patients have been analyzed for cadmium and zinc. Sephadex chromatography was performed on soluble extracts from these tissues. In samples from 19 patients a cadmium-binding protein was found. The mean cadmium content of kidney in this group was higher than the corresponding value for all 40 patients. A molecular weight of 10 to 12,000 was estimated for the cadmium-binding protein by Sephadex chromatography. Isoelectric focusing resolved two peaks with pl 4.8 and pl 6.0, the OD254/OD280ratio for both peaks being about 5. These data indicate that humans without known occupational exposure to cadmium do have a cadmium-binding protein similar to metallothionein in their liver and kidney.
Assuntos
Cádmio/metabolismo , Rim/metabolismo , Fígado/metabolismo , Metaloproteínas/análise , Cromatografia em Gel , Exposição Ambiental , Humanos , Focalização Isoelétrica , Ligação Proteica , Espectrofotometria Atômica , Zinco/metabolismoAssuntos
Encéfalo/ultraestrutura , Compostos de Etilmercúrio/metabolismo , Mercúrio/metabolismo , Compostos de Metilmercúrio/metabolismo , Compostos Organometálicos/metabolismo , Acetilcolinesterase/metabolismo , Animais , Núcleo Celular/enzimologia , Crescimento/efeitos dos fármacos , Isótopos de Mercúrio , Microssomos/enzimologia , Mitocôndrias/enzimologia , Bainha de Mielina/enzimologia , Terminações Nervosas/enzimologia , Proteínas do Tecido Nervoso/metabolismo , Radioisótopos , Ratos , Frações Subcelulares/enzimologia , Succinato Desidrogenase/metabolismoRESUMO
Methyl mercury has been shown to interact with protein synthesis in vivo and in vitro. In the present paper a brain postmitochondrial supernatant was used for studies in vitro. Inorganic mercury (Hg2+) was shown to be more potent inhibitor of protein synthesis than methyl mercury, puromycin or cycloheximide. The inhibitory effect of methyl mercury was potentiated by puromycin. It is thus possible that methyl mercury causes disintegration of polysomes in brain cells.
Assuntos
Encéfalo/metabolismo , Compostos de Metilmercúrio/farmacologia , Proteínas do Tecido Nervoso/biossíntese , Animais , Encéfalo/efeitos dos fármacos , Cicloeximida/farmacologia , Sinergismo Farmacológico , Leucina , Masculino , Mercúrio/farmacologia , Mitocôndrias/metabolismo , Puromicina/farmacologia , Ratos , Ratos EndogâmicosRESUMO
Uptake of elemental mercury after inhalation (3.5 mg/m3) and the activity of catalase in brain, liver, kidney and blood were investigated in rat, hamster, guinea-pig, and normal and acatalasemic mice. The uptake of mercury in the species investigated varied considerably, being highest in the two strains of mice, followed by rat and hamster, and lowest in the guinea-pig. The uptake seemed to be more dependent on pulmonary ventilation than on the activity of catalase. The two strains of mice were exposed to a wide range of mercury concentrations in air (0.002-3.5 mg/m3). The content of mercury in brain, liver and kidney was linearly dependent on the mercury concentration in the air, whereas in blood this relationship was exponential. At the lower concentrations of mercury in the inhaled air, the mercury level in blood was significantly lower, and in kidney higher in the acatalasemic mice compared to the normal ones. In acatalasemic mice the mercury content in liver was higher at all concentrations investigated, whereas in brain no difference between the two strains was found.
Assuntos
Catalase/metabolismo , Mercúrio/metabolismo , Acatalasia , Animais , Carga Corporal (Radioterapia) , Cricetinae , Cobaias , Pulmão/fisiologia , Mesocricetus , Camundongos , Ratos , Ratos Endogâmicos , Especificidade da Espécie , Distribuição TecidualRESUMO
Uptake of mercury by brain after intravenous injection of elemental mercury was investigated in the rat. Catalase activity was inhibited by aminotriazole either by intraperitoneal injections affecting catalase in most tissues of the animal or by intraventricular injections affecting catalase in the brain selectively. Uptake of elemental mercury by rat brain was not influenced by intraperitoneal administration of aminotriazole resulting in 50% inhibition of brain catalase. However, when the inhibitor was injected intraventricularly in concentrations to give a 50% inhibition of brain catalase, it was shown that the mercury uptake by the brain was significantly decreased. In the latter case when only brain catalase was inhibited and the supply of elemental mercury to brain was maintained, mercury uptake by brain was proportional to the activity of catalase in brain tissue and to the injected amount of elemental mercury. Contrary to the intraventricular injection of aminotriazole, in animals receiving aminotriazole intraperitoneally prior to elemental mercury injection, we suggest that the lower activity of brain catalase is compensated by an increased supply of elemental mercury caused by the generally lower oxidation rate in the animal. This view is supported by the finding that mercury uptake by liver increased due to aminotriazole intraperitoneally although activity of catalase was depressed.
Assuntos
Encéfalo/metabolismo , Catalase/análise , Mercúrio/metabolismo , Amitrol (Herbicida)/farmacologia , Animais , Encéfalo/enzimologia , Catalase/antagonistas & inibidores , Masculino , Ratos , Ratos EndogâmicosRESUMO
The effects of methylmercury (MeHg) on cytoplasmic microtubules in cultured neuroblastoma cells, glioma cells, and fibroblasts were compared. Neuroblastoma cells appeared to be more sensitive to disruption of microtubules by MeHg than the glioma cells or fibroblasts; cellular concentrations of mercury after MeHg were also higher in neuroblastoma cells. Recovery of microtubule structure was monitored in cells after removal of MeHg; addition of the chelating dimercaptosuccinic acid (DMSA) increased reassembly of microtubules. During MeHg treatment and early recovery, microtubule integrity was dependent on cellular mercury concentrations. However, after prolonged DMSA exposure, mercury appeared to reenter the cell, without causing dissociation of microtubules.
Assuntos
Compostos de Metilmercúrio/toxicidade , Sistema Nervoso/efeitos dos fármacos , Animais , Fibroblastos/patologia , Imunofluorescência , Glioma/patologia , Microtúbulos/efeitos dos fármacos , Neuroblastoma/patologia , Ratos , Succímero/farmacologia , Fatores de TempoRESUMO
A single dose of 10 mg methylmercury chloride per kg body weight was given to 30 days old rats and to adult rats (180-200g)(. This resulted in brain levels of 1.4-2.2 micrograms Hg/g wet weight. In the young rats electron microscopic morphometry showed swelling of the granule cells. The extent of changes was more pronounced in the cerebellar hemispheres than in the vermis and flocculus. At 7 days after giving the methylmercury the granule cells appeared to have returned to normal. Methylmercury produced both light and electron microscopic changes in cerebellar neurons of adult (180-200 g) rats 3 days after dosing. 2.5-10% of the granule cells appeared dark and condensed in toluidine blue stained semithin sections of perfusion fixed and plastic embedded material. In control animals the comparable percentage never exceeded 1. By electron microscopic morphometry the dark cells proved to be shrunken to 70%, whereas the remaining light granule cells were swollen to 130% of the normal cell volume. The heterochromatin and mitochondrial volumes per cell remained constant in both dark and light cells from methylmercury treated animals. In the purkinje cells from both young and adult rats, geometrical changes in the cisternae of the granulated endoplasmic reticulum were evident. The swelling and shrinkage of the granule cells is supposed to be due to impaired electrolyte control and the disorganized granulated endoplasmic reticulum of the Purkinje cells may be related to the deleterious effect on protein synthesis.
Assuntos
Cerebelo/efeitos dos fármacos , Compostos de Metilmercúrio/toxicidade , Fatores Etários , Animais , Cerebelo/patologia , Cerebelo/ultraestrutura , Microscopia Eletrônica , RatosRESUMO
Liver and kidney samples obtained from 76 autopsies were analyzed for cadmium and zinc content. The patients had died of various internal diseases. None of them had any known occupational exposure to cadmium. A record was made of age, sex, place of residence, diagnosis, and smoking habits of each patient. The results showed no significant correlation between cadmium accumulation and hypertension or cardiovascular disease. There was, however, a significantly higher kidney cadmium level in smokers than in nonsmokers.