Biomedical subjects

M Cikrt

Publications and source records attributed to M Cikrt.

At least 19 recordsLinked to original sources

PubMed1992

Distribution and excretion of cadmium and nickel after simultaneous exposure and the effect of N-benzyl-D-glucamine dithiocarbamate on their biliary and urinary excretion.

A rat model for combined exposure to cadmium and nickel is presented that involves the administration of drinking water containing these elements over a period of 90 d. Coadministration of these two ions in drinking water leads to brain levels of both elements that are significantly higher than results from the administration of equal doses of the metals individually. The enhanced biliary excretion of cadmium in rats given sodium N-benzyl-D-glucamine dithiocarbamate (BGDTC) is almost twice as great in those animals given cadmium and nickel as in those animals given cadmium only. The excretion of nickel is reduced by the administration of this chelating agent. Although equal amounts of nickel and cadmium were administered to these animals, liver and kidney cadmium levels were approximately 100 times greater than the corresponding nickel levels. The results suggest that combined exposure to these elements may lead to enhanced levels of nickel and cadmium in the brain and a level of nervous system damage not predictable from information obtained under conditions of exposure to only one of these elements.

Administration, Oral↗

PubMed1992

The study of exposure to cadmium in the general population. II. Morbidity studies.

An epidemiological study was performed to assess whether environmental pollution by cadmium as found in cadmium polluted areas of CSFR (Pribram and Frýdek-Mistek) is associated with changes in biological indicators of renal dysfunction in non-occupationally exposed population groups. Polluted areas were chosen on the basis of existing sources of Cd emission. The city of Prague was selected as a control area. Environmental monitoring (Cd in air, dust fall and soil) did not confirm significant contamination of selected areas. It was found that Cd levels in urine (Cd-U) of inhabitants living in areas chosen as Cd-contaminated were significantly higher than in the control area. Differences in concentrations of Cd in blood (Cd-B) levels between individual areas were not significant. No significant differences between the study populations were noted in the urinary excretion of low molecular weight proteins (beta 2-microglobulin, retinol binding protein) and albuminuria. However, total proteinuria and aminoaciduria in persons living in Pribram area was significantly higher. This area suffers from combined contamination by cadmium and lead. In smokers of both sexes the Cd-B levels were significantly higher in all areas, no significant differences were found in Cd-U levels. However, it was found that in smokers there is higher percentage of persons excreting more than 0.9 micrograms Cd.g-1 creatinine in urine. Consumption of home-grown vegetable and fruit in Cd-polluted areas led to significantly higher levels of Cd-B and Cd-U and total proteinuria. The results of the study show that smoking and food seem to be the most important sources of Cd intake in non-occupationally exposed populations. In spite of the fact that environmental monitoring does not reveal a significant contamination of selected areas by Cd, Cd-U levels confirmed that population living in these areas is really exposed to Cd.

Cadmium↗

PubMed1991

Influence of age and time of administration of dithiocarbamate analogues on cadmium retention in rats.

In the present study the influence of age and time of chelation therapy on cadmium retention in 6-, 11-and 14-day-old rats and in 6-week-old rats has been investigated. Chelating agents N-benzyl-dithiocarboxy-D-glucamine (BDCG), sodium N-(metho-xybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) and N-methyl-N-dithiocarboxy-D-glucamine (MDCG) were administered intraperitoneally to three different groups at a dose of 1 mmol kg-1 body weight on two occasions following 115mCd intraperitoneal administration; immediately and after 24 h; after 24 h and 48 h; or after 48 h and 72 h. The 115mCd retention in the whole body and organs was determined 6 days after cadmium administration. Chelation therapy very effectively reduced cadmium retention in the whole body and organs, MeOBDCG being the most effective. The effects of chelating agents were significantly more pronounced in older than younger animals and in the case of early rather than late administration. The highest fraction of cadmium administered was retained in the liver, where also the strongest effect of chelation therapy was observed. Mobilized cadmium was excreted almost exclusively by the faecal route.

Aging↗

PubMed1991

Dithiocarbamate analog N-(4-methoxybenzyl)-N-dithiocarboxy-D-glucamine reduces the retention of ingested cadmium in rats.

This study was performed to evaluate the effect of oral and intraperitoneal treatment with N-(4-methoxybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) after a single oral administration of 115mCd to 6-week-old rats. Oral treatment reduced the retention of 115mCd in the whole body, gut, liver and kidney by 5, 3, 4 and 3 times respectively, and intraperitoneal treatment reduced the retention by 7, 2.5, 16 and 4.5 times, respectively. This finding is new, since it was believed that oral dithiocarbamate treatment would increase the toxicity and absorption of ingested cadmium.

Administration, Oral↗

PubMed1991

Sodium bis(hydroxyethyl)dithiocarbamate reduces acute lung tissue damage induced by cadmium in rats.

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.

Animals↗

PubMed1991

Mobilization of aged cadmium from isolated rat hepatocytes by sulfhydryl chelators.

Isolated hepatocytes appear to be a suitable in vitro model for the testing of the efficacy of chelating agents. In this study hepatocytes were isolated from rats exposed to CdCl2 (50 mg Cd2+/l) in drinking water for 3 months. The cells were incubated in a Krebs-Henseleit buffer for 2 hrs and the cytotoxicity was assessed using 5 types of parameters. N-benzyl-D-glucaminedithiocarbamate (BGDTC) and meso-2,3-dimercaptosuccinic acid (DMSA) were tested. Individual chelators in various concentrations were added to the incubation medium at the beginning of the experiment (t = 0). The concentration of Cd in the extracellular fluid was measured every 30 mins using flame AAS. Exposed hepatocytes did not show the signs of damage. Both chelators did not exhibit any cytotoxic effect. BGDTC was found to be efficient in the mobilization of Cd, while DMSA was ineffective.

Animals↗

PubMed1990

[Chelating agents].

The problem of chelating agents used as antidotes in intoxications with metals is intensively studied during the past 20 years. Due to the complex nature of the action of these substances in the organism their investigation is a typically interdisciplinary problem. The submitted review gives the theoretical background of the formation of chelate in the organism, the strategy of research of new substances is discussed and findings on the main groups of chelating agents used in human medicine are summarized.

Animals↗

PubMed1990

The study of exposure to cadmium in the general population. I. Autopsy studies.

From 1982 to 1986 samples of materials (liver tissue, kidney cortex) were collected from 438 autopsies in Prague. The age of persons was over 50 years and residence time in the area was at least 10 years Concentrations of Cd and Zn were determined in the kidney cortex and the liver tissue using the AAS method. On the basis of the Questionnaire for Relatives, data on smoking habits, and occupational history of the investigated persons were obtained. The results of the study confirmed that the concentration of Cd in analyzed tissues did not exceed values reported in the literature for people of similar age living in Cd uncontaminated areas. In smokers significant increase of Cd in the kidney cortex was found in all age and sex groups. The body burden of Cd in smokers is significantly higher.

Adult↗

PubMed1990

Biological monitoring of human exposure to metals.

Biological monitoring of exposure to metals and metalloids involves not only determination of these elements in selected body fluids and tissues but, in some cases, also determination of a certain biochemical indicator which signalises the presence of the monitored element in the organism. Biological monitoring of occupational exposure to metals has a long tradition whereas biological monitoring of exposure in general environment has developed more intensively only in the past two decades. New information about the toxic effect of some metals and metalloids and about their kinetics of absorption, distribution and excretion in experimental animals, and particularly in man, is necessary for elaborating suitable biological exposure tests. Of current interest is also the movement of persistent noxae in the environment, seen from the ecologic view point. This report outlines the present state of the problem in Czechoslovakia.

Adult↗

PubMed1989

Mercury-selenium interaction: distribution and excretion of 203Hg2+ in rats after simultaneous administration of selenite or selenate.

In female rats intravenously injected with 203HgCl2 (0.6 mg Hg2+ per kg body wt.) the effect of intraperitoneal administration of selenite or selenate (0.525 mg Se per kg body wt.) on distribution and excretion of 203Hg was studied. The content of 203Hg was lower in kidney and higher in liver and blood in the groups treated with selenate or selenite when compared with rats which received only mercury. The brain content of 203Hg was significantly increased in rats injected with selenite. Both selenium compounds injected immediately after mercury significantly decreased urinary as well as biliary excretion of 203Hg. A transient increase in the rate of biliary excretion of 203Hg during the first 2 h after administration was observed in rats treated with selenate. This finding seems to support the idea that the reduction of selenate to selenite in the body is not rapid but takes at least several hours.

Animals↗

PubMed1989

Cadmium influence on the rat liver.

Influence of cadmium on the intestinal and hepatic tissue of rat was studied in acute injection and oral as well as subchronic and chronic oral experiments with the purpose of better understanding of the penetration mechanisms of cadmium into these tissues. Acute single oral dose of CdCl2 32.5 mg.kg-1 inhibited in vitro the respiration of intestinal scrapings (44%) and in liver slices (25.7%). In combined oral doses of 32.5 mg.kg-1 + 162.5 mg.kg-1 inhibition in the intestine increased with exposure time, while in the liver it decreased. Amount of presumable metallothionein in the liver was approximately ten times higher than that in the intestine. Respiration was measured by a Clark electrode. Binding of cadmium to metallothionein was determined by column chromatography and spectrophotometry. Physiological findings are in agreement with morphological ones. In cases when, following an acute single oral dose, a 50% change was detected in the absorptive jejunal zone, a 10% change was observed in the liver parenchyma. In the case of combined oral dose of 60-70% of absorptive villi zone is damaged by cadmium, which penetrates by passive diffusion into lamina propria and by blood to the liver, where it acts toxically in 30%. Active transport of cadmium after chronic application is preserved. Correlation of physiological and morphological findings was evident.

Absorption↗

PubMed1989

Biliary excretion of mercury and cadmium.

The own kinetic data on the biliary excretion of different mercury species and cadmium are presented. The role of enterohepatic circulation, mechanisms of biliary excretion and mobilization of Cd2+ and Hg2+ with selected chelating agents are discussed. The experimental results are confronted with scarce human data available from own laboratory and literature.

Animals↗

PubMed1988

Distribution and elimination of (14C)-2-ethylhexyl acrylate radioactivity in rats.

The fate of (14C)-2-ethylhexyl acrylate was studied in adult male Wistar rats given an intravenous (i.v.) or intraperitoneal (i.p.) injection of 10 mg/kg (0.054 mmol/kg). The elimination of radioactivity from blood was bi-exponential, irrespective of the route of (14C)-2-EHA administration or the age (weight) of the rats. The first phase half-lives after i.v. and i.p. administration in 4-month-old rats were 30 and 60 min, in 7-month-old rats 115 and 130 min, respectively. The corresponding values for the slow-phase were 5 and 6 h, and 14 and 14 h. Elimination of the radioactivity from tissues followed a pattern similar to that seen for blood. More than half of the administered radioactivity was exhaled as carbon dioxide. Exhalation of unchanged (14C)-2-EHA accounted for only 0.05% (i.v.) or 0.3% (i.p.) of the initial dose of radioactivity. The radioactivity excreted in the urine within the first 24 h post-treatment accounted for 7% (i.p.) or 14% (i.v.) of the initial dose, and only 2% was excreted as thioethers.

Acrylates↗

PubMed1988

Synergistic enhancement of the biliary excretion of cadmium by the simultaneous administration of two dithiocarbamates.

The simultaneous i.p. administration of the two chelating agents bis(2-hydroxyethyl)dithiocarbamate (DEDTC) and 4-carboxamidopiperidinedithiocarbamate (INADTC) to rats given cadmium in their drinking water at a level of 50 mg cadmium/liter for 39 days led to a large synergistic effect on the biliary excretion of cadmium. A much smaller synergistic effect on the urinary excretion of cadmium was also noted. When treated with a similar mixture of chelating agents after a similar cadmium-drinking water exposure of 180 days, rats showed significant decreases in both renal and brain cadmium levels.

Animals↗

PubMed1988

Effect of cadmium on the rat intestine.

The effect of cadmium on rat jejunal mucosa was observed after application of CdCl2 doses: acute single (32.5 mg.kg-1) or combined (32.5 + after 24 h 162.5 mg.kg-1) and chronic (250 mg.l-1, daily consumption 10 ml for 3 months). Inhibition of mucosal respiration, measured by a Clark electrode was 44, 50.4 and 38.4% respectively, as related to 100% of controls. Metallothionein was determined in the mucosa for combined and chronic doses. Electron X-ray microanalysis has shown Cd2+ distribution in dependence on pathological changes: greater regressive changes caused smaller Cd2+ retention. In acute experiments Cd2+ penetrate by passive diffusion through foci of damaged villi into the lamina propria. In crypt absorptive cells with preserved alcalic phosphatase and succinate dehydrogenase activity and in Paneth cells Cd2+ retention was determined. Combined dose of Cd2+ damaged homeostasis and prevented Cd2+ retention. In chronic experiments occurred a diffuse distribution of Cd2+ in the mucosa.

Animals↗

PubMed1988

Distribution and excretion of 74As and 75Se in rats after their simultaneous administration. The effect of arsenic, selenium and combined pretreatment.

The exposure of man to isolated toxic agent in the environment is rather a rare phenomenon. Therefore the study of a combined action of toxic substances is of increasing importance. The excretion and distribution of 74As (500 micrograms As.kg-1 b.wt.; Na74AsO2) and 75Se (525 micrograms Se.kg-1 b.wt.; Na275SeO3) was studied in rats after their separate and simultaneous i.v. injections. After simultaneous administration urinary as well as biliary excretion of 75Se and urinary excretion of 74As was increased in comparison with that in animals injected the radionuclides separately. Simultaneous administration of 74As and 75Se decreased concentration of 75Se in liver and increased concentration of 74As in kidney. In rats drinking water containing As (III) (0.66 mmol.l-1), Se(IV) (0.13 mmol.l-1) or combination As(III) + Se(IV) (at the same concentrations) for 7 or 28 days was studied the excretion and distribution of 74As and 75Se after their simultaneous i.v. injection (at the same concentrations and labelled compounds as mentioned above). The pretreatment with one element or with the combination of both elements significantly modified the distribution and excretion of subsequently administered 74As and 75Se.

Animals↗

PubMed1987

The effect of some chelating agents on the biliary and urinary excretion of manganese in rats.

The biliary excretion of manganese, in rats which have been loaded with manganese via their drinking water, can be significantly enhanced by the administration of the chelating agents: desferrioxamine (DSF), sodium bis(hydroxyethyl) dithiocarbamate (DEDTC), and sodium isonipecotamidedithiocarbamate (INADTC). The effect of these chelating agents on the urinary excretion of manganese was more complex and was found to be dependent upon the level of loading of manganese as well as the individual chelating agent. For animals with drinking water containing 400 mg/liter of manganese, the administration of the chelating agents led to a decrease in the sum of the biliary plus urinary manganese excretion. The results are of special interest in that they show that under some conditions the administration of chelating agents can lead to changes other than those expected.

Animals↗

PubMed1987

The effect of 110mAg on ceruloplasmin oxidase activity in rats.

The effect of single i.v. injection of 110mAgNO3 (0.183 mg Ag+ X kg-1 b.wt.) in rats on the ceruloplasmin oxidase activity (Cp) and copper serum concentration was studied. It was found that Cp activity in the serum decreased to 70% of the control value and simultaneously serum copper concentration decrease to 30% of the control level. In both cases the decrease was independent on the time elapsed after silver administration. Comparing these results with those reported recently in mice Cu deficit in the rat serum was approximately twice higher. This fact is considered to be an inter-species difference. The concentration of copper in the hepatic supernatant significantly decreased (to eight times from control value) after silver injection. Only less than 10% of the total amount of Ag found in whole liver was taken up to hepatic supernatant. GPC analysis of the supernatant (Sephadex G-75) revealed that no Ag-metallothionein fraction is present. On the basis of the results obtained it was concluded that the mechanism of silver inhibition of Cp oxidase activity remains still in question.

Animals↗