B. Kargačin

Simultaneous reduction of radioactive strontium, caesium and iodine retention by single treatment in rats

The effect of a mixture of calcium alginate, iron (III) ferrocyanide and potassium iodide added to rat diet on 85Sr, 137Cs and 131I metabolism and health was investigated in female rats after four weeks of treatment. The retention of these radioisotopes was determined in the whole body and critical organs six days after 85 Sr and 137CS and one day after 131I oral administration. The health effect of the mixture was evaluated by measuring body weights, haematological parameters, concentrations of iron, zinc and manganese in the kidneys, liver and femur, bone parameters (femur composition and morphometry) and by a histopathological examination. The mixture reduced 85Sr retention in the femur 11 times, 137Cs retention in the thigh muscle 102 times and 131I retention in the thyroid 134 times. Treated animals were in good health and the only differences found between the control and experimental rats were slightly lower haemoglobin values in the blood and a slightly lower iron concentration in the liver. It is concluded that the mixture was very efficient for decreasing body retention of three important fission products and that it can be used over long periods without causing adverse health effects.

Gut retention of metals in rats

In sucklings, a high fraction of orally administered metals and radionuclides is retained in the gut. The location of elements in the gut is of interest because of their potential local health effect.The purpose of this work was to evaluate the influence of chelation therapy on gut retention and location of cadmium, mercury, and cerium in-suckling rats. Radionuclides115mCd,203Hg, and141Ce were administered orally to 6-d-old rats. Chelating agent Zn-DTPA (3.64 mmol/kg) was administered to animals that received115m Cd or141Ce and Na-DMPS (375 μmol/kg) to those that received203Hg, immediately and 24 h or 24 and 48 h after radionuclide administration. Radio-activity was determined in the whole body and gastrointestinal tract 6 d later. Both early and delayed chelation treatment very effectively reduced whole body retention, and this was mainly owing to reduced gut retention. Although chelation therapy reduced gut retention of administered radionuclides 3–30 times, the site of metal accumulation and retention in the intestine remained unchanged. For all 3 radionuclides, both after early and delayed therapy, the site of metal accumulation was always the lower part of small intestine—ileum.

Influence of dietary ingredients on the body retention of strontium, cadmium and mercury in suckling rats

Six-day-old suckling rats were artificially fed over 8 h with cows milk or a mixture of rat food ingredients (fish meal, sunflower meal, alfalfa, cane molasses and premix) labelled with 85Sr, 115mCd or 203Hg. Whole-body radioactivity was determined in a double crystal scintillation counter every 24 h over a 6-day period. Carcass, gut, liver and kidney retention were determined at the end of the experiment. Relative to pups that were fed on cows milk, administration of the mixture of the solid dietary ingredients caused a significant reduction in whole body, carcass and organ retention of all metals and was highest for 203Hg. This indicates that high absorption of toxic metals in sucklings can be reduced by dietary means. Rat food ingredients deserve further consideration because they are non-toxic dietary constituents and might be useful for decreasing the body burden of some metals in conditions of increased environmental exposure.

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.

The Influence of Age on the Effectiveness of DTPA in Reducing 141Ce Retention in Rats

The influence of age on the effectiveness of chelation treatment in reducing retention of radioactive cerium was studied in two- and six-week-old albino rats. 141Ce was administered intraperitoneally, followed immediately and after 24 and 48 hours by intraperitoneal administration of the tri-sodium calcium salt of diethylenetriaminepentaacetic acid--Na3(CaDTPA) at 380 mumol/kg body weight. The whole-body retention was determined 2, 4 and 6 days after radiocerium administration, when the animals were killed and the organ retention was determined. The chelation therapy significantly reduced the whole-body retention of radiocerium. This treatment was however twice as effective in older as in younger animals.

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.

2,3-Dimercaptopropane-1-sodium sulfonate for reducing retention of ingested 203Hg in suckling rats.

The purpose of this work was to determine the efficiency of treatment with 2,3-dimercaptopropane-1-sodium sulfonate (DMPS) for reducing retention of ingested mercuric chloride in suckling rats. The authors wanted to estimate whether the previously mentioned efficacy of oral chelation therapy is related to DTPA only or also applies to other chelating agents. This might be important for establishing treatment for ingested metals and radionuclides in the youngest age group.

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 μmol/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.

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 cows 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.

Effect of cadmium-mobilizing dithiocarbamates on essential trace metal metabolism in rats

The purpose of the present study was to evaluate the effect of three chelating agents N-benzyl-N-dithiocarboxy-D-glucamine (BDCG), N-methyl-N-dithiocarboxy-D-glucamine (MDCG) and sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate monohydrate (MeOBDCG) which were previously found very effective in reducing cadmium retention and enhancing its elimination from the body on concentrations of some essential elements in the liver and kidney in rats and on their urinary excretion.