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Biomedical subjects

K Kostial

Publications and source records attributed to K Kostial.

At least 37 records · Page 2Linked to original sources

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↗

[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↗

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↗

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↗

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↗

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↗

The effect of composite oral treatment for internal contamination with several radionuclides on 131I thyroid uptake in humans.

The efficiency of a composite oral treatment on 131I thyroid uptake was investigated in three adult volunteers. The treatment consisted of 10 g of calcium alginate, 3 g ferrihexacyanoferrate(II), 130 mg of potassium iodide and 5 g of Zn-DTPA. This mixture when administered 30 min before 131I almost completely blocked the 131I thyroid uptake. This indicates that simultaneous administration of other antidotal agents do not cancel or decrease the effect of potassium iodide on 131I thyroid uptake. The finding deserves attention since composite oral treatment is the recommended therapy in cases of accidental environmental exposure to several radionuclides.

Administration, Oral↗

The influence of age on the efficiency of delayed therapy with Ca-DTPA for cerium in rats.

The influence of age on the effectiveness of chelation therapy starting 24 h after cerium administration was studied in 2- and 6-week-old rats. 141Ce was administered IP, followed after 24 and 48 h by IP administration of trisodium calcium diethylenetriaminepentaacetate (Ca-DTPA). The whole body and organ retention of 141Ce was determined 6 days after its administration. The chelation therapy significantly reduced cerium retention in both age groups but was more efficient in older animals. This age-related effect was, however, less pronounced than after immediate treatment with DTPA observed in our previous experiments, indicating that age as one of the factors which influence the efficacy of chelation treatment is probably more important in conditions of early than in conditions of delayed therapy.

Age Factors↗

Age-related efficiency of Ca-DTPA to reduce 141Ce retention in rats.

The study was aimed at evaluating the influence of age on the efficiency of chelation therapy for cerium in case of late administration. The efficacy of trisodium calcium diethylene-triaminepentaacetate (Ca-DTPA) administered as a first dose 48 and 72 h after 141Ce was investigated in 8-week-old and 2-week-old rats. The effect of treatment gradually decreased depending on the time period between radionuclide and chelating agent administration. Higher efficacy of chelation therapy in reducing the whole-body retention of 141Ce in older animals was constantly shown to be independent of the time of administration of chelating agent. The influence of age on the efficacy of chelation therapy was different for various organs and tissues; e.g., for liver and gut chelation therapy it was more effective in older animals, for kidneys it was equally effective in both age groups, while for bone it was more effective in the younger animals. The present results indicate that the effect of age in chelation therapy is influenced by the time of administration of the agent as well as by radionuclide distribution in organs and their availability for chelation.

Aging↗

Reduction of 85Sr, 137Cs, 131I and 141Ce retention in rats by simultaneous oral administration of calcium alginate, ferrihexacyanoferrate(II), KI and Zn-DTPA.

The effect of simultaneous oral administration of a mixture of calcium alginate, ferrihexacyanoferrate(II) and KI and of the chelating agent zinc diethylenetriaminepentaacetate (Zn-DTPA) on the retention of radioactive Sr, Cs, I and Ce was investigated in 7-week-old female rats. The respective antidotes were administered in food during the first three days of the experiment and the radionuclides were administered on the second day of the experiment. The radionuclide retention was determined in the whole body, carcass, gut, liver, kidneys and respective critical organs six days after oral administration of 85Sr, 137Cs, 131I and intraperitoneal administration of 141Ce and one day after oral administration of 141Ce. Simultaneous oral administration of the four therapeutic agents reduced the retention of radioactive Sr, Cs and I administered orally and Ce applied intraperitoneally. Zn-DTPA did not diminish efficacy of antidotes from the mixture nor did the mixture significantly alter the effect of Zn-DTPA. Simultaneous oral administration of calcium alginate, ferrihexacyanoferrate(II), KI and Zn-DTPA might present a convenient method for delayed therapy especially in cases of prolonged increased environmental exposure to several radionuclides.

Administration, Oral↗

The effect of 2,3-dimercaptopropane sodium sulfonate on mercury retention in rats in relation to age.

The effectiveness of DMPS (sodium 2,3-dimercaptopropane-1-sulfonate) in reducing inorganic mercury retention was studied in 2-, 6-, and 28-week-old albino rats. 203Hg was administered IP. The chelating agent DMPS was administered by IP injection at a dose of 250 mumol/kg body weight three times, 1 day after 203Hg administration and at 24 h intervals thereafter. The whole body retention determined 1, 2, 3, and 6 days after 203Hg administration showed that DMPS decreased the body retention of mercury in all age groups, being about twice as effective in adult compared to suckling rats. The reduced effectiveness was due to the reduced efficacy of DMPS in reducing kidney retention in young animals. In other organs the effectiveness of DMPS was not age dependent. These and previous results obtained with different chelating agents and other metals indicate that age might be an important factor in chelation therapy in general.

Age Factors↗

Lower efficiency of DTPA in reducing cadmium retention in suckling rats.

The influence of age on the effectiveness of chelation therapy in enhancing cadmium elimination was studied in 1-, 2-, 8-, and 26-week-old rats. 115mCd was administered intraperitoneally, followed immediately and after 24 hr by an intraperitoneal injection of trisodium calcium diethylenetriaminepentaacetate (DTPA) (600 mumole/kg body wt). The whole body retention determined on the second, fourth, and sixth days of the experiment showed that DTPA greatly decreased cadmium retention in all age groups being about four times more effective in older than younger animals. Determination of 115mCd retention in the gut and organs also revealed that effectiveness of DTPA was lowest for the youngest age group and increased with increasing age. This effect of DTPA was more pronounced in the liver than in the kidney and brain in all age groups. These results indicate that age greatly influences chelation of cadmium and that age might be an important factor in chelation therapy in general.

Aging↗