In vitro prediction of cytostatic drug resistance in primary cell cultures of solid malignant tumours.

The in vitro monolayer proliferation assay (MP-assay) described here enables predictive determination of the efficacy of anticancer drugs considered for clinical application. The assay was designed (1) to achieve a high plating efficiency, (2) to adapt in vitro growth as close as possible to in vivo conditions, and (3) to prove that the cells in vitro correspond with the in vivo tumour cells they were derived from. From 452 freshly explanted or biopsied tumours, 321 (71%) proliferating cultures could be established. To prove malignant origin of the incubated cells each strain was characterised by DNA-cytophotometry for aneuploidy and by immunocytochemistry for marker proteins. Drug potency was determined by comparing the number of living cells in drug-treated cultures with non-treated controls. Drug concentrations in vitro corresponded with those achievable in tumour tissue and thus represented clinically relevant levels. Growth inhibition in vitro was correlated with in vivo tumour response. Two hundred in vitro/in vivo correlations were performed (50 retrospective, 150 prospective). Overall predictive accuracy of the MP-assay was 86%, with correct indication of resistance in 94.5% and of sensitivity in 75.8% (P < 0.001). The results show that the proposed assay is capable of estimating the response probability of cytostatic drugs in individual tumours and thus can contribute to reducing the applications of non-effective drugs and, within limitations, to improving the basis of drug selection.

Secondary combined resistance to the multidrug-resistance-reversing activity of cyclosporin A in the cell line F4-6RADR-CsA.

Multidrug-resistant tumor cells can be resensitized by combined application of the selecting cytostatic drug and a chemosensitizer, such as cyclosporin A (CsA) or a calcium channel blocker. Since clinical trials on the circumvention of multidrug resistance (MDR) with chemosensitizers report disparate results, we investigated whether tumor cells of the MDR phenotype can develop additional resistance to the cytostatic chemosensitizer combination. Thus, the Adriamycin(ADR)-selected, P-glycoprotein-positive MDR Friend leukemia cell line F4-6RADR was exposed to stepwise increased concentrations of CsA at a constant level of 0.05 microgram/ml ADR. The initial CsA concentration (plus 0.05 microgram/ml ADR) to inhibit cell growth of F4-6RADR cells by 50% (IC50) was 0.04 microgram/ml. By continuous incubation for more than 6 months, the IC50 for CsA (at constant ADR) was elevated to 3.6 micrograms/ml (90-fold), thus generating the variant F4-6RADR-CsA. The F4-6RADR-CsA cells were cross-resistant for cyclosporin H (CsH), a non-immunosuppressive derivative of CsA. As shown by immunocytochemistry as well as by the polymerase chain reaction and by Western blotting including densitometry, P-glycoprotein was preserved in the F4-6RADR-CsA variant and was expressed at a 4-fold higher level than in F4-6RADR cells. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis analysis could detect no new proteins in F4-6RADR-CsA as compared to F4-6RADR. Interestingly, resistance of F4-6RADR-CsA cells remained reversible for the calcium antagonists verapamil and dihydropyridine B859-35 (dexniguldipine-HCl), indicating that CsA and these compounds interfere with the P glycoprotein function by different pharmacodynamic mechanisms. Transport studies with [14C]ADR, performed in the presence and absence of chemosensitizers, confirmed the good correlation of P-glycoprotein function with the pattern of resistance found in proliferation assays. Cellular accumulation of [3H]cyclosporin was reduced to 71% of that of the F4-6 controls in F4-6RADR-CsA cells, but remained at the level of controls in F4-6RADR cells. Results indicate that increased amounts of the P-glycoprotein--besides other, perhaps more important mechanisms that are as yet unknown--partially mediate CsA resistance in F4-6RADR-CsA cells. We have designated this new form of resistance "secondary combined resistance" (SCR). The results suggest that at least some clinical cases of insensitivity to chemosensitizers or of relapse after reversing therapy could be explained by SCR, and that resensitizing treatment of tumor patients should be based on the consideration of several chemosensitizers of different pharmacodynamics.

Intracellular localization, vesicular accumulation and kinetics of daunorubicin in sensitive and multidrug-resistant gastric carcinoma EPG85-257 cells.

In the human gastric carcinoma cell line EPG85-257P (parent) induction of resistance to daunorubicin (DAU) was achieved by selection with stepwise increased concentrations of the drug. The new variant was named EPG85-257DAU and was shown to overexpress the mdr1 gene product 170 kDa P-glycoprotein (P-Gp) as demonstrated by immunocytochemistry and mdr1-specific RT-PCR. To investigate the intracellular pathway of DAU the subcellular distribution of this autofluorescent drug was studied in the resistant cells and compared to its chemosensitive counterpart EPG85-257P. When sensitive cells were exposed to DAU the drug rapidly accumulated in the nucleus until cell death. No redistribution of DAU to the cytoplasm was observed. In resistant cells exposed to the drug DAU also accumulated in the nucleus but to a lesser extent than in parent cells. Following exposure, nuclear fluorescence was observed to decrease over a time period of up to 48 h. Six hours after DAU exposure formation of fluorescent vesicle formation started in the perinuclear region and increased continuously. After 48 h nuclear fluorescence was no longer detectable and DAU was located exclusively in vesicles. During this period the vesicles moved from the region of origin to the cell periphery. A pulse chase experiment showed, that vesicles may contain DAU derived from the nucleus. Treatment of EPG85-257DAU cells with DAU in conjunction with the chemosensitizer cyclosporin A (CsA) increased nuclear fluorescence without impairing vesicle formation. Disruption of microtubules by nocodazole led to an accumulation of vesicles in the perinuclear region indicating that microtubules are involved in vesicular transport. Treatment of EPG85-257DAU cells with the actin disruptor cytochalasin B led to accumulation of vesicles in the cell periphery indicating that actin may be involved in exocytosis. Uptake and efflux of DAU and rhodamin (RH) were determined in sensitive and resistant cells using a fluorescence activated cell sorter. Uptake of both compounds was distinctly lower in resistant than in sensitive cells. When resistant cells preloaded for 2 h with RH subsequently were incubated in drug free medium the substance was rapidly released indicating transmembrane transport by P-Gp. In contrast, despite expression of P-Gp in resistant cells no considerable release of DAU was observed for up to 2 h under the same experimental protocol. This indicates that in resistant cells intracellular DAU at least in part may be inaccessible for P-Gp and that vesicular drug transport appears to contribute to DAU resistance by removing intracellular DAU via exocytosis.

Toxoplasmosis and iodine deficiency in Angora goats.

Toxoplasmosis was diagnosed in two goat herds in the Czech Republic. The 1996 outbreak in the herd of Angora goats was associated with abortions and births of weak kids. No apparent signs of toxoplasmosis were observed in the herd of White Short-Haired (WSH) goats reared under similar conditions. Seroprevalences of 60% and 66% tested by complement fixation and indirect fluorescent antibody tests, respectively, were found in the herd of Angora goats during the outbreak of clinical toxoplasmosis. Significantly lower values were recorded in this herd in years 1994 and 1997 and in the herd of WSH goats between years 1994-1996. Iodine deficiency was also demonstrated in the herd of Angora goats in 1996. Goitre was detected by clinical examination in 39% of animals and mean urinary iodine concentration was 8.0+/-4.65 microg per 11. This concentration rose significantly to 15.7+/-5.02 microg per 11 in the subsequent year. Effects of iodine deficiency on clinical manifestation of toxoplasmosis in Angora goats were discussed.

[Carbadox in combination with furazolidone in the prevention of enteral and growth disorders in weaned piglets]. / Karabadox v kombinaci s furazolidonem v prevenci enterálních a rustových poruch u selat po odstavu.

Two feed mixtures were produced, each containing the antimicrobial preparation Carbadox and different amounts of furazolidone. Their fortnightly administration in starters to piglets weaned at the age of 25--31 days prevented mortality and stimulated somatic growth and feed utilization. Premix with a higher content of furazolidone markedly depressed the clinical symptoms of gastro-enteritis and reduced the number of the haemolytic germs of E. coli in the contents of the duodenum and jejunum. The presence of furazolidone in the feed completely eliminated enteral disorders and delayed the onset of the disease, or alleviated its course, in cases of severe diarrhoea, which killed, in the control group, the piglets of the same litter. Weight gains were significantly increased, particularly in the first post-weaning week, the difference from the control being up to 520%. Almost 0.5 kg of the COS 2 starter was saved per 1 kg of piglet live weight gain. Under the current farming conditions of five agricultural enterprises the weight gains during the ten days of the administration of the medicated feed were increased, on an average by 0.84-1.32 kg. In herds where the untreated piglets put on less than 1 kg the gains were increased by 96--124%. It is recommended to administer the new-developed medicated premix to prevent losses due to alteration of the intestinal microflora in early-weaned piglets.

[The effect of furazolidone or carbadox in the starter mixture for early-weaned piglets]. / Pusobení furazolidonu nebo karbadoxu ve starteru pro casne odstavená selata

For a period of 14 days, piglets from six litters, weaned between the 25th and 28th day of age, were fed the COS 2 starter containing either a premix with furazolidone or carboadox of Czechoslovak origin. Bentonite hydrosilicate was used as a carrier in both cases. Furazolidone administered in the dose of 200 mg per 1 kg of feed prevented diarrhoea, insignificantly increased body weight gain, and decreased the consumption of feed per 1 kg of gain from 5.6 kg in the control to 4.0 kg in the test animals. Carbadox administered in the dose of 50 mg per 1 kg of feed suppressed the signs of enteritis in comparison with the control piglets, significantly increased body weight gains, and reduced feed consumption to 1.9 kg per 1 kg of gain. No differences were recorded in the concentration of blood glucose, total protein, and total cholesterol in plasma. The control piglets showed increased parameters of the adrenocortical function. The proportion (percentage) of haemolytic E. coli in rectum was affected neither by carbadox nor by furazolidone; furazolidone suppressed the occurrence of lactoso-negative strains. An insignificant drop of the number of haemolytic E. coki in the duodenum and jejunum of the furazolidone-and carbadox-treated piglets was observed after 14 days. With their clinical effects, the two substances tested manifest themselves as suitable for the reduction of losses in weaned piglets.

[The dependence of vitamin A and E concentrations in blood plasma on nutrition and age of growing pigs]. / Závislost koncentrace vitamínu A a E v krevní plazmé rostoucích prasat na výzive a na veku.

Four experiments (duration 21 to 137 days) were conducted where 112 pigs were divided into ten groups and fed dry mixtures with different content of nitrogenous substances, vitamin A and E. The repeated determination of the content of these vitamins in blood plasma and in liver proved the dependence of the circulating vitamin A first of all on its present alimentary intake; in the case of vitamin E its content is related to the animal age. As sufficient intake of the complete COS mixtures (2.4 mg of retinol . kg-1), in the weaned 4-week piglets the concentration of vitamin A in blood plasma was increasing up to the maximum values. After transition to the complete mixture A 1 (0.6 mg of retinol .kg-1), and particularly after the following switching to SOL mixture (0 retinol content) the concentration of vitamin A decreased significantly (as a rule temporarily) up to the value of 0.6 mumol .1(-1), with sufficient reserve in liver. Lower values were determined only at the absence of vitamin A in A 1 mixture; its content in liver (over the period of 117 days) decreased to the 14% of the state observed when feeding the complete mixture. Animal protein reduction in A 1 mixture led to the decrease in A vitamin level both in plasma and in liver. During one to six weeks after weaning of piglets the concentration of plasma vitamin E decreased approximately by two thirds, and, as a rule, only during the fourth month reached the value of 2.5 mumol .1(-1). The positive effect of the SOL mixture was observed. The increase in the vitamin E supplement in COS 2 mixture by 15 mg to the declared 30 mg reduced the decrease of tocopherolemia after weaning but did not prevent it. One-day starving before slaughter significantly decreased the vitamin A and slightly the vitamin E concentrations in plasma. The results are evaluated with respect to diagnostic applicability to blood plasma examination and with respect to the amount of vitamin supplements added to feed mixtures.

[Current views on the importance of iodine for animals]. / Soucasný pohled na význam jodu pro zvírata.

The study summarizes current experience on the cause and impacts of iodine deficiency, compares the measures to ensure iodine needs and shows the consequences in human population and farm animal. The hazard of iodine deficiency is increasing at present due to underevaluation of mineral nutrition importance, restrictive measures in feeding techniques, further due to stronger effect of natural and anthropogenic goitrogens from feedstuffs and drinking water, higher iodine consumption due to higher performance and load caused by large-scale technologies. These facts have impact on health state of cattle which is confirmed by increased occurrence of functional disorders of the thyroid gland in young farm animals, and consequently affect iodine deficiency in human population as the major source of iodine in child s food is milk and milk products.

[Inorganic anions with a potential goitrogenic effect in drinking water supply for humans and animals]. / Anorganické anionty s mozným strumigenním vlivem v pitných a napjecích vodách.

The levels of inorganic anions (NO3-, NO2-, SO(2-)4, F- and HPO(2-)4 with the following average values (mg/l) were determined isotachophoretically in 82 samples of potable water for humans and animals: 39.7 +/- 53.1 for nitrates, min. 0.0 - max. 363.3; 0.206 +/- 0.954 for nitrites, min. 0.0 - max. 7.82; 37.5 +/- 32.4 for chlorides, min. 0.0 - max. 137.9; 74.2 +/- 74.1 for sulfates, min. 4.2 - max. 369.2; 0.208 +/- 0.138 for fluorides, min. 0.032 - max 0.605 and 0.350 +/- 1.197 for phosphates, min. 0.0 - max. 17.4 (Tabs. I-IV). Within the set of samples examined, 22.0 of samples exceeded the limit value of nitrites; the respective values of nitrites, chlorides, sulfates and phosphates were 13.4, 6.1, 2.4 and 1.2. None of the samples exceeded the limit value of fluorides. 34.1% of samples complied with the value recommended by the standard for nitrites. Nitrate concentrations in drinking water for cows were compared with urine iodine content in some cows in the total of 398 urine samples from 14 iodine content in urine was recorded at some localities. Correlation analysis proved this relationship to be statistically highly significant (P < 0.01), Tab. VIII. The values of nitrate and iodine contents at DYJ locality are expressly different (Tab. VII).

Pharmacokinetics of sodium humate in chickens.

Free or liposome-encapsulated sodium humate was administered to chickens intracardially, orally or subcutaneously and the following principal pharmacokinetic parameters were determined using the MW Pharm software for two-compartment models: elimination half-life (t1/2 el), steady state distribution volume (Vdss), blood clearance (Cl), maximal drug concentration (Cmax), time required for appearance of Cmax (tmax), area under the curve (AUC) and bioavailability (F). Blood clearance of liposome-encapsulated sodium humate was higher than that of free sodium humate regardless of the way of administration. On the other hand, the elimination half-life was longer after the extravascular than after the intracardial administration. Cmax values indicate that the penetration of sodium humate from the injection site into blood circulation is very slow. Biological availability of sodium humate also depended on the way of administration and dosage form. Aside from the intracardial administration, the highest bioavailability was found after subcutaneous administration of free sodium humate.

[Adaptation of chickens to feed with a reduced content of nitrogen compounds]. / Adaptace kurat na krmivo se snízeným obsahem dusíkatých látek

In two experiments carried out with 280 broiler chickens, 20 to 30 days old, the authors studied the effect of a sudden and stage-like change-over from a diet with 20% of nitrogen compounds to a diet with 10% of nitrogen compounds. In both variants of the experiment there was a slowing down of the weight increment, increase of the adrenal weight, reduction of the weight of spleen, of Fabricius weight, heterophilia and lymphopenia. A stage-like change-over of the diet had a more moderate effect. In the activity of the liver enzymes amino transferases of aspartate, alanine and succine-dehydrogenase -the authors found a different character of the changes in both variants of the experiment. The reduction of nitrogen compounds in the diet of growing chickens causes also changes which are typical for an increased adrenocortical activity.

[Use of feed mixture with a higher content of plant proteins in piglets during the weaning period]. / Uplatnení krmné smesi s vyssím obsahem rostlinných proteinu u selat v období odstavu

Two experiments with 56 piglets and pilot trial on 84 piglets were performed to demonstrate that it is possible to replace the complete mixture for early piglet weaning (COS-1, or COS-2) by an experimental mixture without fish meal, with a higher proportion of soya and maize, supplemented by lysine and methionine; this mixture is to be fed to piglets in the weaning period. The weight gain dropped in both basic experiments after weaning, especially in the group with a higher content of nitrogenous matters in the diet. No significant inter-group differences were found in the activity of enzymes in serum and in liver, nor were they found in the adrenocortical activity.

[Adrenocortical activity in pigs in relation to nutrition, body weight mycobacteriosis and pre-slaughter stress]. / Adrenokortikální aktivita prasat ve vztahu k výzive, telesné hmotnosti, mykobakterióze a predporázkovému stresu.

In 115 pigs divided into 10 groups, with different nutrition levels or with experimentally evoked atypical mycobacteriosis, during the experiments or at slaughter the concentration of 11-hydroxycorticosteroids (11-OHCS) in blood plasma, relative weight of adrenal glands and liver were determined. The increase in adrenocortical function was proved in the cases when the body weight was significantly influenced by malnutrition, and then in the pigs at slaughter, even after relatively careful handling. No changes were found in the course of mycobacteriosis. The relative weight of adrenal glands in slaughtered pigs of lower body weight was higher than that in the pigs of the same age, but of higher body weight. On the other hand, the slaughtered pigs of higher body weights tended to have higher 11-OHCS concentrations. The prolonged stay of the pigs in slaughter houses before bleeding did not result in the increased 11-OHCS levels. The quality of meat was not affected.

[The importance of the infective dose, nutritional value of the feed and vitamin content for the susceptibility in pigs to Mycobacterium intracellulare]. / Význam infekcní dávky, nutricní hodnoty krmiva a obsahu vitamínu pro vnímavost prasat k mycobacterium intracellulare.

The influence of infectious dose and nutrition on the pig susceptibility to Mycobacterium intracellulare, serotype 4, 8, was studied with 48 pigs--crossbreds LW X X L--divided into four equal groups. All groups of pigs were fed ad libitum by the mixture consisting of maize, wheat, barley, soybean meal, salt lick and MKP 1 mineral feed supplement. Individual groups were given different levels of meals of animal origin and biofactor supplements containing vitamins A, D2, B2, B12 and niacin. Single per os administration of the infectious dose of Mycobacterium intracellulare amounted to 0.01 or 0.1 mg of mycobacterial culture per one kg of live weight. The extent of patho-anatomical findings depended on the infection intensity. The infectious dose of 0.01 mg of the culture resulted in the changes in the form of exudative lymphadenitis with characteristic caseous degeneration in lymphatic glands only in three out of 24 pigs, i. e. in 12.5%. A tenfold dose of mycobacteria caused caseous lesions in the mandibular and intestinal glands in 50% out of 22 infected animals. The result of complex examination of the lymph glands proves the favourable effect of biofactor supplement on the resistance in pigs, particularly those infected with lower mycobacterial doses. Mycobacteriosis was proved in all experimental pigs fed the mixture containing no biofactor supplement. In the group of animals fed the mixture with biofactor supplement the result was positive in 66.6% of infected animals. It was observed that the biofactor supplement also had a positive influence on active excretion of M. intracellulare by faeces. In pigs infected with high dose of mycobacteria this excretion was proved in 27.2% of animals. In the pigs fed the mixture containing biofactor supplement, regardless of the infectious dose and amount of animal proteins, no elimination of mycobacteria by faeces was observed. Out of 14 pigs with the microscopic finding of tuberculosis in the lymph glands, the reaction with an induration diameter larger than 10 mm was found in eight animals, i. e. 57.2%, after intradermal tuberculinization with purified avian tuberculin after 74 days from infection.

[Biochemical changes in the blood of pigs after exertion]. / Biochemické zmeny krve prasat po svalové zátezi.

15-minute forced movement of pigs evoked after 18 to 24 hours an increase in the activity of creatine kinase, lactate dehydrogenase and aspartate aminotransferase and in the level of non-esterified fatty acids in blood serum. The changes in the enzyme activity following muscular strain were individual. The pig group with higher average weight gains, fed the diet containing 284 g of crude protein per 1 kg, showed greater differences in the muscular enzymatic activity than the animals with lower weight gains, fed the diet containing 260 g crude protein per 1 kg. Single administration of vitamin E (six hours before strain) did not subdue the elution of enzymes from tissues after muscular strain. Another important strain factor was the fixation of pigs by trying them outside their own group.

Urinary iodine level as an intake indicator in dairy cows.

Urinary iodine concentrations were determined in 672 dairy cows of 22 herds. Less than 20 micrograms per L, 20 to 50 micrograms per L, 50 to 100 micrograms per L and more than 100 micrograms per L were found in 27.5, 24.6, 16.8, and 31.3% of the cows, respectively. In terms of the ICCIDD grading, moderate iodine deficiency was recorded in 68.9% and normal iodine intake in 31.3% of the cows. The mean urinary iodine concentrations were 94.8 micrograms per L at the peak of the lactation period (n = 300), 82.3 micrograms per L immediately before drying off (n = 122), 92.5 micrograms per L in the cows fed summer rations (n = 267), and 79.2 micrograms per L in those fed winter rations (n = 405). The differences in mean values were nonsignificant. Urinary iodine concentrations were examined in the herd LOS in cows fed iodine-supplemented (LOS E) or nonsupplemented (LOS C) rations. Mean concentrations were 316.2 micrograms per L for LOS E (n = 46) and 52.3 micrograms per L for LOS C (n = 41). The difference was highly significant (P < 0.01). The status of the group LOS C was classified as a medium iodine deficiency. The mean iodine concentrations at the peak of the lactation period and immediately before drying off were also significantly higher (P < 0.01) in this group. The supplementation of iodine resulted in an increase of urinary iodine concentration and, in terms of ICCIDD, the increase of iodine intake to the normal range. Normal intake and moderate, medium and serious deficits were found in three, two, one, and four herds, respectively. Special attention should be paid to herds showing higher grades of iodine deficiency.

[The use of dried grape press cake in pig fattening]. / Uplatnení susených hroznových výlisku u prasat ve výkrmu.

In dried grape press cake the content of crude nutrients and ash, overall sugar, amino acids, alpha-tocopherol and gross energy was determined. In biological experiments with pigs (total of 109 animals) 10% of mixture A1 or SOL was replaced by the same amount of dried crushed grape press cake, without affecting negatively the weight gains and consumption of mixtures per unit of weight gain. Nutritional effects of grape press cake are a subject of discussion and comprise three factors: higher content of enrgy (fat and sugars) in mixtures containing press cake, anti-oxidation effect of press cake and the effect of tocopherols on the metabolism of basic nutrients.

[Carotene and fluorometrically determined vitamin A levels in the blood plasma of cows in relation to gravidity and type of feeding]. / Hladiny karoténu a fluorometricky stanoveného vitamínu a v krevní plazme krav ve vztahu k brezosti a typu krmení.

From January to June we determined the concentration of vitamin A and carotene in the blood plasma of 66 high-pregnant cows and cows 23 to 54 days after calving. Seasonal changes and a decrease in the content of both substances before delivery were proved. In field conditions of three farms it was determined that the haylage type of winter feeding was better than the silage type of winter feeding in view of provitamin A supply. The concentration of carotene in blood was always higher with haylage feeding as well as that of vitamin A during the period of high lactation. Regardless of that the level of vitamin A in dairy cows in April and May was lower by almost a quarter compared with feeding fresh green forage in June. The results reveal that the suitable time for assessing the sufficiency of vitamin A supply in cows is the time starting one month after the beginning of lactation. The usability and accuracy of the fluorometric method for determining vitamin A, while respecting the interference caused by phytofluen and beta-carotene, have been proved.

[Evaluation of adverse effects of the wood-impregnation substance Pentor 70]. / Zhodnocení zdravotní nezávadnosti drevoimpregnacní látky Pentor 70

A hundred and ten days direct contact of pigs with wooden grates impregnated with Pentor 70 did not result in the arising of any obvious changes or reactions in the skin or in the lowering of efficiency. A per os intake of feed mixture with a content of 3 p. c. of sawdust impregnated with Pentor 70 resulted in the lowering of efficiency and in the arising of pathological changes in the digestive tract and in the livers. In experiments performed with rats, the contact with the impregnated sawdust and also the combination of the contact and per os acceptance resulted in changes in the respiratory organs of rats and in young rats in mortality. A limiting factor regarding the use of Pentor 70 in premises intended for pigs is the danger of gnawing impregnated wooden objects.

[The effect of sodium huminate on cadmium deposition in the organs of chickens]. / Vliv humátu sodného na ukládání kadmia v orgánech kurat.

In the chickens with an experimental load of cadmium chloride (CdCl2 x 2.5 H2O) at a rate of 0.3 mg per bird and day the effect was investigated of various forms of sodium humate administration in free and/or liposomal form as exerted on cadmium concentrations in liver, kidneys and muscle. The values of the field below the curve (AUC) showing average cadmium concentrations in the investigated tissues of chickens (liver, kidneys, muscle) in the given time interval of 1-14 days were higher in all cases in the tissues of chickens which received cadmium, that means in the groups K2, P1, P2, P3 and P4 in comparison with the negative control (K1). Statistical significance of differences was demonstrated in liver and kidneys. No statistically significant changes were observed in the muscle. Simultaneous administration of cadmium and HuNa (P1), and also other methods of HuNa administration (P2, P3, P4) reduced cadmium concentrations in liver, kidneys and muscle statistically significantly only in P1 group in liver and kidneys. Cadmium concentrations on days 1, 3, 8 and 14 after termination of experimental treatments were lowest in the liver of the 1st control group (negative control), which received HuNa only (Tab. I). Five-day administration of 0.3 mg cadmium (positive control) influenced its values statistically highly significantly in the liver of all experimental groups in all the investigated time intervals (Tab. I). The first experimental group, which received cadmium simultaneously with HuNa had the statistically significantly lower values on days 3, 8 and 14 in comparison with the positive control. Simultaneous administration of cadmium and HuNa reduces cadmium availability and so its absorption and deposition in liver are lower. Cadmium concentrations on days 1, 3, 8 and 14 after termination of experimental treatments were lowest in the kidneys of chickens of the 1st control group (negative control), which received HuNa only (Tab. II). Five-day cadmium administration (positive control) influenced its values in the kidneys of all experimental groups highly statistically significantly in all the investigated time intervals (Tab. II). The first experimental group which received cadmium simultaneously with HuNa had the statistically significantly lower values on days 3, 8 and 14 in comparison with the positive control. Simultaneous administration of cadmium and HuNa reduced cadmium availability and so its absorption and deposition in liver are lower. Cadmium concentrations in the muscle on days 1, 3, 8 and 14 after termination of experimental treatments were lowest in the 1st control group (negative control), which received HuNa only (Tab. III).(ABSTRACT TRUNCATED AT 400 WORDS)