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Biomedical subjects

E Sabbioni

Publications and source records attributed to E Sabbioni.

At least 91 records · Page 5Linked to original sources

Heavy metal uptake and intracellular binding in isolated gill preparations of Mytilus galloprovincialis L.

An in vitro study was performed on the uptake and subsequent binding to protein of heavy metals in isolated gill preparations of Mytilus galloprovincialis. The metals used in the study were Cd, Zn, Hg, V, Cr, Te, Tl, As and Tc. Experiments were conducted for one hour and the disappearance of metals from the water correlated with final gill-metal concentrations. Distribution of metal between 105,000 g cytosol and pellet was determined, as was the association of each metal with cytosol protein following gel-filtration chromatography. Results indicate that all metals are accumulated by the gills but that the uptake kinetics vary with each metal. Similarly, the association of each metal to protein varied for each type.

Animals↗

Health and environmental implications of trace metals released from coal-fired power plants: an assessment study of the situation in the European Community.

In the European Community (EC) the anticipated increased use of coal for power production will lead to an increase in the release of trace metals into the environment. This release seems unlikely to cause toxicological effects through the food chain, but there may be a possibility of a direct impact on man through inhalation. There are, however, many areas of uncertainty which need to be clarified by further research before a definitive assessment can be made.

Coal↗

Human exposure to heavy metals. Rare earth pneumoconiosis in occupational workers.

A male subject exposed for many years to rare earth (RE)-containing fumes and dusts emitted from carbon arc lamps in photoengraving laboratories was investigated to rule out RE pneumoconiosis. While chest x-ray films showed a severe pulmonary fibrosis, clinical analysis showed obvious high RE concentrations in the pulmonary and lymph node biopsy specimens compared with the corresponding tissues of 11 unexposed subjects. In addition to other elements, levels of thorium (Th), which is generally present as an impurity of RE compounds, were also determined to estimate the radiation dose which may be involved in inducing pneumoconiosis. The results show that the levels of Th are more than two orders of magnitude lower than the maximum permissible concentration for occupational exposure to natural 232Th, suggesting that the long-term accumulation of RE in the lungs played a role in the pathogenesis of the observed pulmonary fibrosis of the worker.

Biopsy↗

Biliary and gastrointestinal excretion of chromium after administration of Cr-III and Cr-VI in rats.

Rats treated intravenously with 51Cr-labelled sodium chromate, 0.1 or 100 microgram Cr/rat, excreted more 51Cr into bile in a 2-hr period than did the animals given equal amounts of chromium in the trivalent state. Distinct patterns of hepatic intracellular distribution of the radiotracer were also observed. In the Cr-VI rats over 50% of the liver chromium was present in the supernatant fraction whereas in the Cr-III rats almost all the liver radioactivity was localized in the cell organelles. Fractionation of bile on Sephadex G-75 demonstrated binding of chromium to low-molecular weight substances. It is suggested that complexes of chromium with low-molecular weight components of liver cytosol are involved in the passage of this element from the liver to bile. A low cytosolic content of diffusable Cr-complexes associated with the incorporation of a large fraction of liver chromium in cell organelles may be a factor contributing to the low rates of 51Cr biliary excretion in the animals given Cr-III. 24 hr after the injection of 51Cr to bile duct-ligated rats appreciable levels of radiotracer were found in the gastrointestinal tract. The animals given Cr-VI exhibited significantly higher values of chromium content in the gut than those treated with Cr-III.

Animals↗

Organ/tissue disposition of thallium in pregnant rats.

The placental transfer of thallium was studied in rats treated with a toxic dose of thallium sulphate (10 mg Tl/kg b.wt. p.o.), as well as in animals injected intraperitoneally with 201Tl-labelled thallium in amounts as low as 2 micrograms Tl/rat. Rapid uptake and retention of thallium in both maternal and fetal organs were observed. The administration of potassium ferrihexacyanoferrate II (100 mg/kg b.wt. twice daily by gavage) to rats acutely intoxicated with thallium on day 17 of pregnancy resulted in significant decrease of thallium concentrations in various maternal tissues including brain, in the placenta as well as in the fetal liver and brain. Potassium ferrihexacyanoferrate II also reduced the mortality of pregnant animals in the 72-h interval after the intoxication.

Animals↗

Intracellular interaction and biotransformation of arsenite in rats and rabbits.

The accumulation of arsenic with time in tissues of rats and rabbits was determined by neutron activation analysis (NAA). Rats showed a steady increase in the As-concentrations with age, whereas in rabbits it was nearly the same for adults and in young animals. The metabolism of arsenic was studied in both animal species after i.p. injection of 50/micrograms As/kg b.w. as 74As labelled arsenite. Eight tissues, as well as blood and urine, were analysed for 74As content after 16 and 48 hours. The binding of 74As to hematic and intracellular components and the chemical forms of arsenic in tissues and urine were investigated. In the plasma and the RBC-fraction of the rabbit, the As concentration decreased during the first two days, while in the rats it only disappeared from the plasma, but was retained in the RBC-fraction. Liver, kidney and lung of rabbits with the highest As concentrations at 16 and 48 hours showed a rapid clearance of As in the first 48 hours. In the corresponding tissues of the rats, the rate of decline was significantly lower, due to the higher binding of 74As to tissue constituents. Poor binding of As to plasma proteins was seen in rabbits while in rats it was totally bound to this fraction. In the RBC, liver and kidney cytosols, however, the affinity of As for intracellular proteins was higher in both animal species but characterized by a rate of binding different between the two animal species. The amount of dimethylarsinic acid (DMA) in the tissues was significantly lower in the rat than in the rabbit, reflecting the total amount of diffusible arsenic, which was also much lower in the tissues of rats than in rabbits.

Animals↗

Long-term occupational risk of rare-earth pneumoconiosis. A case report as investigated by neutron activation analysis.

A case of rare-earth (RE) pneumoconiosis is described and discussed. A man working in a lithographic laboratory as a photoengraver, and exposed to the smoke of cored carbon arc lamps over a period of 46 years developed an interstitial pneumoconiosis. Neutron activation analysis (NAA) of eight rare-earths (La, Ce, Nd, Sm, Eu, Tb, Yb and Lu) in lung and lymph node biopsies showed an abnormally high amount of these elements in comparison to the corresponding values of 11 autopsied for unexposed subjects. The estimated radiological dose due to the inhalation of natural thorium, as calculated from NAA of thorium in the biopsies, tends to exclude the effect of ionizing radiation in the pathogenesis of lung fibrosis. Effects of other potential pathogenetic agents such as coal or heavy metal dusts, other than RE, irritative agents such as nitrous and hydrofluoric vapours originated during the photoengraving process, are also discussed. The findings strongly suggest that a relationship exists between the pneumoconiosis diagnosed and the occupational exposure to rare-earth dusts calling attention to proposals for maximum permissible concentration limits of occupational exposure to RE in air.

Animals↗

Placental transfer and retention of 201Ti-thallium in the rat.

Placental transfer of thallium was evidenced in rats treated with a single intraperitoneal dose of 2 micrograms 201T1-labelled thallium/rat on the 13th day of pregnancy. Both maternal and fetal organs showed remarkable thallium retention, approx. 10% of the dose being unexcreted 8 days after injection. The highest thallium accumulation was found in maternal muscle and brain tissues. Fetal brain exhibits higher thallium uptake and faster decay rate of thallium levels than maternal brain. It is suggested that the reduced activity of the mechanisms regulating ion movements and composition of nervous tissue and the immaturity of the blood-brain barrier play a role in the peculiar pattern of thallium kinetics in the developing rat brain.

Animals↗

Environmental biochemistry of current environmental levels of heavy metals: preparation of radiotracers with very high specific radioactivity for metallobiochemical experiments on laboratory animals.

Environmental toxicology research on dose-response relationships of heavy metals requires experiments on laboratory animals exposed to "low doses" of trace elements which should reflect "present or actual environmental levels" characteristic of polluted environments. Unfortunately no criteria exist to establish the "low doses" to which laboratory animals must be exposed, in practice the choice of the level used is made in an almost arbitrary manner. In order to define the "present environmental levels" of heavy metals which should be administered to laboratory animals an approach is suggested, based upon knowledge of the concentrations of trace elements in the diet, air and food as well as the fractions absorbed. Today daily intakes of trace elements by man are of the order of few micrograms or nanograms thus requiring the use of extremely sensitive analytical techniques to determine the very low amounts of heavy metals in tissues and cellular components. In these fields of research the use of radiotracers with very high specific radioactivity appears particularly advantageous but requires considerable care during their preparation and use. The first part of this paper deals with a definition of the ranges of concentrations of trace elements which should be used for metabolic studies on laboratory animals when they are exposed via different routes such as ingestion, inhalation in injection; the second part describes the production of radiotracers with very high specific radioactivity by proton activation in the cyclotron and by neutron irradiation in the nuclear reactor. Their use to label present levels of heavy metals under conditions adapted for biochemical purposes, as well as the preparation of different metal-labelled chemical species is also reported. Particular attention is directed to quality control of the radiotracer solutions which are administered to the animals including those of radioactivity concentrations, radioisotopic purity, radiochemical purity, carrier content and chemical impurities.

Animals↗

Biotransformation and intracellular binding of arsenic in tissues of rabbits after intraperitoneal administration of 74As labelled arsenite.

The fate of arsenite was studied in rabbits injected i.p. with 1 microgram As/kg body wt as 74As labeled AsO2-. Eight tissues plus plasma and urine were analyzed for 74As content at different times. Arsenic was rapidly metabolized and poorly retained in the tissues. The main metabolite present in urine and plasma was dimethylarsinic acid. Sixty percent of the dose was excreted via urine and 6% with feces during the first day. In plasma arsenic was present mainly in a diffusible form, showing a very poor binding affinity to plasma proteins. Chromatographic separations and membrane ultrafiltrations showed that in liver and kidney cytosols, arsenic was significantly associated to proteins. The diffusible fraction disappeared within 48 h. The fraction of arsenic bound to proteins was suggested to be inorganic arsenic whereas the methylation process was closely related to the elimination and the detoxification of inorganic arsenic.

Animals↗

Relations between iron and vanadium metabolism: in vivo incorporation of vanadium into iron proteins of the rat.

In vivo experiments with 48V and 59Fe radiotracers were performed to study the association of V with Fe proteins. Each male rat was injected ip with 10 micrograms 48VO2+ and then with 1 microgram 59Fe3+ to label Fe-containing proteins. The radioactivities incorporated were measured in plasma transferrin, red blood cell hemoglobin, liver ferritin, partially purified heart myoglobin, and liver mitochondrial and microsomal cytochromes b and c and ferriporphyrin. Liver ferritin can bind V in vivo similarly to plasma transferrin, as shown by gel filtration and immunoprecipitation. Negligible amounts of 48 V were incorporated into hemoglobin, partially purified myoglobin, and cytochromes b and c. These findings suggest that the nonenzymatic Fe-containing proteins may be involved in the V metabolism.

Animals↗

Intracellular interaction and metabolic fate of arsenite in the rabbit.

Rabbits were treated with single doses of 50 micrograms AsO2-/kg b.w. by IP injection. At 48 h, 83.0 +/- 2.1% of arsenic is excreted via the urine. Also in blood the clearance of arsenic is rapid. Liver, kidney, and lung, among the tissues tested, show the highest concentration of arsenic at 5, 16, and 48 h after injection. Arsenic was found to be present at subcellular levels mainly in the nuclear and soluble fractions of the above-mentioned tissues. Chromatographic studies performed by gel filtration have shown that in plasma and in lung cytosol, arsenic is present, associated mainly to low molecular weight components, whereas in liver and kidney cytosol it is prevalently recovered in the fractions corresponding to the high molecular weight components. This different interaction of arsenic with molecular components was shown to influence the metabolic fate of this compound in the rabbit.

Animals↗

Biliary excretion of vanadium in rats.

The biliary excretion of vanadium was studied in bile duct cannulated rats at various times after the iv administration of a single dose of 48V-labelled pentavalent vanadium. The tissue disposition, hepatic intracellular distribution and binding of 48V to plasma, bile and liver components were also investigated. During the first 6 hours after the injection of V, 0.9 to 30 microgram/kg, less than 2 per cent of the dose was excreted into the bile and up to 20 per cent of vanadium was eliminated in urine. The bile flow was markedly decreased in rats cannulated 24 hours after the injection of V, 30 microgram/kg, while higher doses produced signs of severe toxicity immediately after the administration. Evidence was also obtained that a concentration gradient triggers the passage of vanadium from plasma to the liver, where only a fractional amount becomes available from canalicular excretion, due to the extensive binding of the metal to organelles and other tissue ligands.

Animals↗

Relationships between iron and vanadium metabolism: the association of vanadium with bovine lactoferrin.

Bovine milk was incubated simultaneously with 48VO2+ and 59Fe3+ ions. The lactoferrin was separated by ion exchange gel chromatography on CM Sephadex C-50 resin. Sephacryl 200 gel filtration of the lactoferrin-containing fractions, from ion exchange chromatography was carried out to dertermine the proportions of 48V and 59Fe radioactivities associated with macromolecules of the size of lactoferrin. It was found that 48V was incorporated into lactoferrin, the milk protein which contains iron. This suggests that lactoferrin may play a role in the bioavailability of vanadium during lactation, as vanadium is an essential element for the growth of some animal species. More generally, the vanadium binding properties of lactoferrin further support previous findings on the possible biochemical role of Fe-containing non hemoproteins in the metabolism of vanadium.

Chromatography, Ion Exchange↗