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Biomedical subjects

K Kostial

Publications and source records attributed to K Kostial.

At least 19 recordsLinked to original sources
PubMed1995

Reduction of lead retention by mono-3-methylbutan-1-yl meso-2,3-dimercaptosuccinate in suckling rats.

The mono-3-methylbutan-1-yl (monoisoamyl) ester of meso-2,3-dimercaptosuccinic acid (Mi-ADMS) was previously found to be superior to meso-2,3-dimercaptosuccinic acid (DMSA) in mobilizing cadmium and mercury deposits in young and adult mice and rats. It was also tested to mobilize lead in and adult mice. It was also tested to mobilized lead in adult mice. The purpose of this study was to evaluate the ability of Mi-ADMS to chelate lead at a very young age, in sucking rats. Lead was applied intraperitoneally at the dose of 5 mg kg-1 in the form of lead acetate to six-day-old rats. Treatment with DMSA and Mi-ADMS was administered orally at the dose of 0.25 mmol kg-1, either as early (0.5 and 24 h) or a delayed (4th and 5th day after lead application) therapy. At the end of the experiment (6th day) lead was determined by atomic absorption spectrometry in the skeleton, liver, kidney and brain of the animals. Results showed that Mi-ADMS was more efficient than DMSA after early application in reducing the skeletal, kidney and brain content of lead. After delayed application it was either (skeleton and kidneys) or better (brain) than DMSA. There was no statistically significant influence of either chelator on liver lead content. The major finding is that Mi-ADMS at low doses causes a much higher reduction in brain retention of lead in sucklings than DMSA. This is important because the brain is considered to be the target organ of lead toxicity in the youngest age group.

Animals↗
PubMed1994

Monoisoamyl meso-2,3-dimercaptosuccinate as a delayed treatment for mercury removal in rats.

Monoisoamyl meso-2,3-dimercaptosuccinate (Mi-ADMS) was found to be superior to meso-2,3-dimercaptosuccinic acid (DMSA) in decreasing the body burden of 203Hg in rats under conditions of early treatment. In this experiment Mi-ADMS was used as late treatment for mercury removal. Albino rats aged 6 weeks and 7-day-old sucklings received a single intraperitoneal injection of 203Hg (as nitrate). Two weeks later they were treated with DMSA or Mi-ADMS (0.25 mmole/kg bw) on two consecutive days. The radioactivity in the carcass (whole body after removal of the gastrointestinal tract), liver, kidneys and brain was determined by solid crystal gamma scintillation counting six days after chelation therapy administration (3 weeks after 203Hg application). Both chelators reduced the body burden of mercury compared to controls. The effect of Mi-ADMS was superior to DMSA treatment in older rats for decreasing carcass and kidney retention, and in suckling rats for decreasing carcass, liver, and kidney retention. They were equally effective in decreasing brain retention in older rats and had no effect on brain retention in sucklings. The efficiency of Mi-ADMS in reducing the body burden of mercury was generally higher than the efficiency of the DMSA treatment. Therefore, Mi-ADMS deserves further attention as a late treatment for mercury removal.

Aging↗
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

Dietary calcium and blood lead levels in women.

Nutritional factors are known to influence metabolism and toxicity of several metals in animal experiments, but relevant human data are scarce and inconclusive. In this work, we tested the hypothesis that dietary calcium influences lead metabolism in humans. Blood lead concentrations were used as indicators of lead exposure and metabolism. Two groups of peasant women living in similar conditions in two different regions in Yugoslavia (100 in each) were chosen as subjects for this purpose. In region A, the dietary calcium intake was about 940 mg, and in region B about two times lower, i.e., 450 mg/day. The average blood lead concentration was significantly lower in women from region A (69 micrograms/L) than from region B (83 micrograms/L). Our results support the assumption that adequate calcium intake might be one of the preventive measures for decreasing lead absorption. This new evidence, sought for some time by nutritionists and toxicologists, needs further international confirmation.

Adult↗
PubMed1991

Reversibility of the effects of lead on the reproductive performance of female rats.

Potential reversibility of the reproductive effect of lead was studied in female albino rats after cessation of oral exposure to 7500 ppm lead as acetate in drinking water. Females mated and gave birth to their first offspring during 9 weeks of lead exposure. They then continued or discontinued exposure, were mated for the second time, and had their second offspring during a longer exposure (20 weeks) or after a period without lead. Food consumption, body weights, and fertility index were not altered irrespective of the exposure conditions. In the first and especially in the second offspring of exposed females, survival rates, litter sizes, and body weights of newborn and 11-day-old pups were decreased. Offspring born to dams in which exposure had been stopped were not different from controls. It was concluded that the adverse reproductive action of lead is reversible after withdrawal of the female from exposure.

Animals↗
PubMed1991

Factors influencing the efficiency of chelation therapy.

The purpose of the present study was to obtain new data on the effect of age, route, dose and time of metal and chelating agent administration on the efficiency of chelation therapy. The experiments were performed on 1-2 and 6-week-old rats which received radioisotopes of metals--203Pb, 115 mCd, 203Hg and 141Ce intraperitoneally or orally. Chelating agents calcium ethylenediaminetetraacetate (CaEDTA), calcium and zinc diethylenetriaminepentaacetate (CaDTPA, ZnDTPA), 2,3-dimercapto-propane-sulfonate-1 (DMPS), dimercaptosuccinic acid (DMSA) and sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) were administered twice by intraperitoneal or oral administration as early (immediately and 24 hr after metals) or delayed treatment (24 and 48 or 48 and 72 hr after metals). The animals were killed six days after metal administration and the retention was determined in the whole body, carcass and gut. After intraperitoneal administration of metals and chelating agents chelation therapy had much lower efficacy in younger than older animals. After ingestion of metals oral chelation therapy was more effective in younger than older animals. In suckling rats the treatment effectively reduced metal retention and this was mostly due to decrease in gut retention. This treatment in sucklings was also very effective in condition of late administration. In older rats early oral DMPS treatment after 203Hg ingestion is contraindicated since it increases significantly mercury retention while DMSA and ZnDTPA treatments reduced mercury retention. Delayed oral treatment with ZnDTPA and DMSA caused increased cadmium retention in older rats and decreased retention in sucklings. Opposite to results with CaDTPA, MeOBDCG was effective in reducing cadmium retention also when given as delayed treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1989

Effect of a metal mixture in diet on the toxicokinetics and toxicity of cadmium, mercury and manganese in rats.

The purpose of this work was to determine whether a metal mixture added to diet influences the toxicokinetics and toxicity of some elements. The metal mixture (MM) used in these experiments was ash (slag) from a coal gasification plant. The effect of this mixture (5 percent in diet) on the toxicokinetic and on the acute or subchronic toxicity of Cd, Hg, Mn was determined in rats of different ages. Rats were exposed for five weeks in toxicokinetic and six weeks in acute toxicity experiments. Sucklings were exposed through their mothers, which received the MM in diet over the pregnancy and lactation period. In toxicokinetic studies, half of the animals additionally received Cd, Hg or Mn (100, 50 or 2000 ppm, respectively) in drinking water. In subchronic experiments, six-week-old albino rats of both sexes were given MM in the diet and Cd, Hg or Mn in drinking water for 16 weeks. In toxicokinetic studies, 115mCd, 203Hg or 54Mn were administered orally or intraperitoneally to mothers and pups. Exposure to MM had no effect on the absorption, retention and organ distribution of these elements determined six days after radioisotope administration. In acute toxicity studies, exposure to MM in diet had no effect on LD50 values obtained eight days after oral administration of Cd, Hg or Mn to rats of different ages. In subchronic experiments, the effect of individual metals (Cd, Hg or Mn) was similar in animals with and without simultaneous exposure to the metal mixture (only a slight potentiation of a few health-effect parameters of cadmium was noticed in some animals). It is concluded that oral exposure to MM in the diet had almost no effect on the toxicokinetics and toxicity of Cd, Hg and Mn. This could be explained by the low level or low bioavailability of elements from MM, by the metal-metal interaction within the mixture or by the choice of health effect indicators determined. These results are presented as one of the potential approaches for studying the health effect of a metal mixture as occurring in the environment.

Aging↗
PubMed1989

[The effect of lead exposure on pathohistological changes in the liver and kidney in relation to age in rats].

Histopathological alterations in the liver and kidneys were examined in adult female rats and in their offspring form two matings after oral exposure to 7500 ppm lead (acetate) in drinking water. The length of exposure was up to 20 weeks. To estimate the reversibility of the effects in a number of exposed females lead administration was discontinued five weeks before their second breeding with unexposed males (the recovered group). In the group of exposed adult females histopathological changes in parenchymal organs were analogous to those seen in their pups from the first (shorter exposure), and second offspring (longer exposure to lead). Fatty and/or hydropic degenerative changes in the liver and kidneys and haemosiderosis of the liver were observed in both adult females and their young. In the liver of exposed pups the presence of numerous large foci of extramedullary erythropoiesis was also detected. In the kidneys of exposed adult females non-specific chronic inflammatory changes were seen. In the group of recovered females, after discontinuation of oral exposure to lead, histopathological findings indicated the reversibility of morphological changes. In their "recovered" pups the findings were also almost normal. It may be concluded that young rats are more susceptible to adverse action of lead than their mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Dietary treatment for decreasing 141Ce body burden in immature rats.

The purpose of this work was to evaluate the effect of prolonged (immediate or delayed) administration of dietary additives to suckling rats on the absorption and retention of radioactive cerium in the body. The experiment was performed on 6-day-old suckling rats. According to dietary treatment the animals were divided into three groups. Each group was artificially fed over 8 h for 6 or 12 days on one of the diets: the first group of animals was fed milk, the second group was given ingredients of rat diet and the third received milk during the first 2 days of the experiment and the ingredients of rat diet afterwards. At the end of the artificial feeding period the pups returned to their mothers and suckled overnight. On the 1st day of the experiment the food was labelled with 141Ce. Whole body radioactivity was determined in a double crystal scintillation counter every 48 h over a 12-day period. Half of the animals from each group were killed 6 days after 141Ce administration and the other half after 12 days. At these intervals retention was determined in the gut, liver, kidneys and femur. The early and delayed administration of rat diet ingredients--fish meal, sunflower meal, alfalfa, cane molasses and premix--greatly reduced whole body retention. The early treatment was more efficacious than the delayed one. The reduction was mostly due to decreased gut retention but organ retentions were also lower. The results obtained indicate that by prolonged (immediate or delayed) administration of some dietary means the retention of radioactive cerium in sucklings can be significantly decreased.

Animals↗
PubMed1987

Oral Zn-DTPA treatment reduces cadmium absorption and retention in rats.

This work was performed to evaluate the possibility of using early oral diethylenetriaminepentaacetate (DTPA) therapy for decreasing absorption and retention of cadmium. Albino rats (6 days and 6 weeks old) were used. 115mCd was administered orally. Zn-DTPA was also given orally (3.64 mmol/kg) immediately after 115mCd and 24 h thereafter. Radioactivity in body and organs was determined 6 days later. In sucklings this treatment decreased whole body and gut retention 7-9 times and kidney and liver retention 2-3 times. In older rats it decreased whole body, gut and organ retention 4-5 times. This finding deserves attention since it is generally believed that DTPA is not indicated for early treatment, i.e. while the toxic metals or radionuclides are still in the gastrointestinal tract.

Administration, Oral↗
PubMed1987

Reduction of 141Ce absorption in suckling rats.

The influence of diet or its ingredients on 141Ce absorption and retention was investigated in six-day-old rats. Animals were fed over 8h with cow's milk, rat diet or a mixture of rat diet ingredients (fish meal, sunflower meal, alfalfa, cane molasses and premix) labelled with 141Ce. Whole-body radioactivity was determined in a double crystal scintillation counter every 24 h over a six-day period. Gut, liver, kidney and femur retention and cerium distribution in the gut was determined at the end of the experiment. Compared to milk diet, administration of rat diet or ingredients caused respectively 3 and 7.5 times lower whole body retention. Carcass retention was reduced by rat diet or ingredients 2-3 times and intestinal retention 3 and 8 times respectively. Irrespective of the dietary treatment the main site of cerium intestinal retention was the ileum. Our present results indicate that some compounds of rat diet might be considered as a means of reducing cerium absorption and intestinal retention in the very young.

Animal Feed↗
PubMed1987

Oral Zn-DTPA therapy for reducing 141Ce retention in suckling rats.

In neonatal rats DTPA reduced the intestinal retention of cerium ingested as an additive in its chloride form to milk. It also reduced retention of absorbed cerium. A similar decrease of cerium retention in gut and whole body was obtained after simultaneous or 24 hours' delayed DTPA administration.

Animals↗