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Biomedical subjects

M Cikrt

Publications and source records attributed to M Cikrt.

At least 37 records · Page 2Linked to original sources

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

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

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

The effect of CdCl2 and AgNO3 pretreatment on the distribution of 110mAg+ in rat liver.

The distribution of 110mAg in the elution fractions obtained from gel filtration (Sephadex G-75) of the supernatants of rat liver homogenates was studied. 110mAgNO3 was administered i.v. at the doses 0.183 and 0.912 mg Ag+ . kg-1 . b . wt.and rats were killed 30 min after the administration. Differential centrifugation of the homogenates was performed to determine 110mAg+ distribution in subcellular structures of hepatocytes. The effect of CdCl2 and AgNO3 pretreatment (2 s.c. injections of 2.5 mg . kg-1 during 48 h) was investigated and results were compared with those obtained without pretreatment. It was found that AgNO3 pretreatment does not affect 110mAg+ distribution in the elution fractions and the major part of the metal is concentrated in the high-molecular-weight protein fraction. On contrary, after CdCl2 pretreatment almost all 110mAg+ is bound in the metallothionein (MT) fraction. Differential centrifugation revealed the main portion of the metal in nuclei and cell membranes and only small amount in lysosomal supernatant. After CdCl2 pretreatment the content of 110mAg+ in supernatant considerably increases. Results confirm the affinity of silver to MT and moreover show that this metal probably does not significantly induce the MT synthesis in the liver tissue.

Animals

Effects of dithiocarbamates on cadmium distribution and excretion in chronically exposed rats.

One month after termination of a 3-mo exposure of rats to cadmium (Cd in drinking water at a concentration of 50 mg/l), the effects of dithiocarbamate analogs on the excretion and distribution of the cadmium were determined. Sodium salts of three dithiocarbamates [sodium bis(hydroxyethyl) dithiocarbamate, DEDTC; sodium N-methyl-D-glucamine dithiocarbamate, MGDTC; and sodium 4-carboxamidopiperidine dithiocarbamate, INADTC] were given to rats ip 2 times at 2.46 mmol/kg. In the following administration of the first injection of DEDTC, cadmium excretion via the urine amounted to 15.8 micrograms and via bile amounted to 124.4 micrograms Cd. Following administration of MGDTC, the urinary and biliary excretions of cadmium were 14.5 and 47 micrograms, respectively, while in the case of INADTC the corresponding values were 23.6 and 7.9 micrograms cadmium. In control animals the urinary and biliary excretion per 12 h reached 0.09 and 0.12 micrograms Cd. Gel permeation chromatography (GPC) analysis of bile revealed differences in the distribution of Cd in the elution fractions after the first injections of the individual dithiocarbamates. For all three dithiocarbamates, significant decreases of the concentrations of cadmium in the liver and kidney were found. DEDTC (but neither of the other compounds) increased the concentration of cadmium in the brain from control levels of 49 +/- 5 ppb to 105 +/- 16 ppb.

Administration, Oral

Structural effects in the dithiocarbamate-enhanced biliary excretion of cadmium.

The dithiocarbamate enhancement of the biliary excretion of cadmium in rats loaded with cadmium (by either the oral or sc route) was found to be strongly dependent on the structure of the groups attached to the nitrogen atom of the dithiocarbamate moiety. Those dithiocarbamates containing hydroxyl-bearing attached groups were found to be capable of causing the greatest enhancement of the cadmium content of the bile. For the compounds of this type that were examined, this enhancement of biliary cadmium content varied from 30-fold to over 2000-fold. No enhancement of the biliary excretion of cadmium was found subsequent to the administration of sodium diethyldithiocarbamate, though this compound is known to cause a significant increase in the fecal excretion of cadmium.

Administration, Oral

Biliary excretion of 110mAg and its kinetics in the isolated perfused liver in rats.

The biliary excretion of 110mAg in rats after i.v. administration of an aqueous solution of 110mAgNO3 (4.57 micrograms; 16kBq per rat) was studied for a period of 24 hours. The maximum rate of excretion was reached in 30th minute after the metal administration and over 70% of the silver dosed was excreted during 24 hours. Using the method of isolated perfused liver it was observed that 110mAg is rapidly taken up in the liver. During the five minutes period of the perfusion less than 50% of silver administered was found in the perfusion medium. In following minutes the level of the metal in the medium remained approximately constant. It was suggested that the rate of excretion of silver and its high uptake in the liver tissue is in connection with an unusual binding of it in the bile.

Animals

Biliary excretion and organ distribution of 14C radioactivity after 14C-2-ethylhexyl acrylate administration in rats.

Rats were intravenously administered (14C)-2-ethylhexyl acrylate at the dose 10 mg/kg or 50 mg/kg b. w. Biliary excretion of 14C-radioactivity was followed in 1-3 hour intervals within the first 24 hours after administration. The rats were then sacrificed and distribution of 14C-radioactivity was followed in some organs. Highest radioactivity was found in liver, less in the kidneys and the least in the brain. A significant increase of bile flow was observed. In the 24-hour intervals 2.2% of the dose was eliminated via bile at both dosages, most of it (83%) during the first 3 hours.

Acrylates

The dependence of biliary methylmercury secretion on liver GSH and ligandin.

The biliary secretion of methylmercury was investigated in male rats which were given i.p. 400 mumoles/kg azathioprine or 96 mumoles/kg benziodarone 2 hr after the i.v. injection of 5 mumoles/kg MeHgCl. A group of rats were given 400 mg/kg trans-stilbene oxide (TSO) for 4 days before treatment with 10 mumoles/kg MeHgCl. A common link between these three compounds is their interference with ligandin. Azathioprine is a competitive inhibitor of glutathione S-transferase, benziodarone is covalently bound to ligandin and TSO is an inducer of liver ligandin. Although only azathioprine depletes liver GSH stores, both azathioprine and benziodarone inhibited the biliary secretion of methylmercury. As there is published proof that the reaction of MeHg+ with GSH does not require enzymatic help, the inhibitory effect of azathioprine and benziodarone confirms the role of ligandin in the transport of methylmercury or its GSH complex. However, the biliary secretion of methylmercury was increased only slightly by TSO pretreatment, but when 2 hr after the injection of MeHgCl animals received 2 mmoles/kg GSH, secretion increased twice as much in TWO pretreated than in control rats. This indicates the dual dependance of biliary methylmercury secretion on liver GSH and ligandin.

Animals

Analysis of the renal tissue of a woman chronically exposed to cadmium.

In a 61-year-old woman, who had been exposed for 20 years to cadmium in the production of Ni-Cd batteries, nephrectomy of the contracted kidney was performed. The removed kidney was examined histologically and the cadmium concentration was determined in the cortex (44.97 micrograms g-1) and in the medulla (7.71 micrograms g-1). The homogenates of the renal cortex and medulla were subjected to gel filtration on Sephadex G-75. In the cortex, as well as the medulla, cadmium was predominantly found in the low-molecular (metallothionein) fraction, but in the cortex, Cd content in this fraction was six times higher than in the medulla. The determination of SH groups and proteins in high- and low-molecular fractions indicates an induction of the metallothionein formation primarily in the renal cortex.

Cadmium

The effect of interaction between subsequent doses of MeHgCl or HgCl2 on the biliary excretion of mercury from each individual dose.

The biliary excretion and organ distribution of mercury was investigated in male rats which received mercuric chloride (HgCl2) (0.65 mg/kg Hg2+) or methylmercury chloride (MeHgCl) (2 mg/kg Hg) i.p. and 48 h later the same compound i.v. Mercury was labelled with 203Hg either in the first or second injection. In controls saline was substituted for unlabelled mercury. In one experiment rats pretreated with HgCl2 were given Me203HgCl 48 h later. The biliary excretion and organ distribution of 203Hg were not influenced by the injection of cold MeHgCl given before or after Me203HgCl or by HgCl2 given 48 h after 203HgCl2. HgCl2 given 48 h before the injection of 203HgCl2 or Me203HgCl significantly decreased biliary excretion of 203Hg despite increased 203Hg levels in blood and liver.

Animals

Manganese: a review of occupational and environmental toxicology.

The following topics are dealt with in this brief review concerning the hygienic and toxicologic aspects of manganese: Occurrence, production, uses; experimental pathology; clinical toxicology; occupational and environmental hygiene aspects of human exposure. The preventive measures outlined: reduction of dust concentration to comply with the established MAC value, in extreme situation even with the use of personal protection; preventive pre-employment examinations to exclude from work all individuals with liver and kidney lesions, blood dyscrasia, organic CNS lesions and progressive lung diseases; elaboration of suitable exposure tests, especially the method of hair analysis, to ensure the biological monitoring of environmental exposure to manganese.

Animals

The effect of sodium diethanolamine dithiocarbamate on distribution and excretion of Cd in rats drinking Cd-containing water.

The effect of sodium diethanolamine dithiocarbamate (DEDTC) on the distribution and excretion of cadmium was studied in three sets of rats whose drinking water contained cadmium at three different concentrations (5, 10 and 50 mg Cd.l-1) for a period of three months. DEDTC administration (500 mg.kg-1, ip) in all exposed groups significantly increased the biliary excretion of cadmium. With the exception of animals drinking water containing the lowest concentration of CD (5 mg.l-1) the urinary excretion was also increased.

Animals

Biliary excretion of lead in rats drinking lead-containing water.

In three groups of rats, drinking lead-containing water (at 100, 250 and 2500 mg lead (Pb)/l) for 80 days, biliary excretion of Pb was studied. In comparison with a control group (0.05 +/- 0.04 micrograms Pb/ml) biliary excretion of Pb in the exposed groups reached 0.08 +/- 0.01, 0.20 +/- 0.04 and 1.46 +/- 0.09 micrograms/ml, respectively. In rats receiving 2500 mg Pb/l, i.v. administration of CaEDTA (0.2 mumol/kg body weight) significantly decreased biliary Pb excretion and increased the concentration of Pb in the kidneys.

Animals

Biliary bilirubin in rats and exposure to metals.

After cannulation the bile duct of unexposed rats, changes in bilirubin concentration in the samples of bile collected were observed. During the first hour after the cannulation the bilirubin concentration decreased remaining constant until about the 3.-4. hour and then continuously increased upto the 24. hour when the experiment ended. The final concentration was about 4 fold higher than between the 1.-4. hour after the cannulation. This could explain a large variation in values reported by various authors. This fact significantly complicated the studies on effect of exposure to heavy metal salts on changes of bilirubin concentration in bile and relationship among bilirubin concentrations in the bile fractions 1, 2 and 3. In the bile of unexposed rats comparable bilirubin concentrations were found in the bile fractions 1 and 2. The preliminary experiment with HgCl2 application to rats revealed that in the fraction 3 might be a higher bilirubin concentration than in the fractions 1 and 2, the latter ones being lower than in the bile of unexposed rats. The hypothesis was suggested that the bile fraction 3 was composed from yellow pigments liberated from compounds forming the fractions 1 and 2 with additional amount of pigments originated during disturbed protoporphyrin biosynthesis of their degradation by the metals.

Animals

Hygienic-toxicological aspects of exposure to lead. A critical review.

This review on hygienic, toxicologic and ecologic aspects of environmental burden of lead deals with the following topics: occurrence, production and use of lead; metabolism of lead and experimental toxicology of lead; toxicity of lead to man; hygienic and ecologic aspects of lead pollution. Lead ore mining and processing, production of lead-acid batteries and combustion of gasoline containing tetraethyl-lead as an anti-knock ingredient constitute at present the most important sources of lead pollution. The last named source of lead pollution in urban atmosphere is most hazardous to human health. Attempts to reduce this health hazard include use of additive-free gasoline, or replacement of tetraethyl lead by other anti-knock agents, e. g. by tetraethylcopper. The experiments with the use of organic compounds of manganese have failed to succeed. The possibility of biological monitoring of occupational and nonoccupational exposures to lead is discussed in detail in this review.

Anemia