Effects of dietary levels of phosphorus and calcium on the comparative behaviour of strontium and calcium.
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Animals↗
Biomedical subjects
K Kostial
Publications and source records attributed to K Kostial.
The influence of temperature on acetylcholine synthesis in the superior cervical ganglion of the cat.
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Acetylcholine↗
The influence of low temperature on acetylcholine and potassium sensitivity of the superior cervical ganglion.
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Acetylcholine↗
Combined treatment with a new biscarbodithioate C9G2DTC and BGDTC for mobilizing cadmium deposits in rats.
The cadmium mobilizing efficiency of a combined treatment with a novel cadmium chelating agent disodium N,N'-bis(D-glucosyl)-1,9-nonanediamine-N,N'-biscarbodithioate++ + (C9G2DTC) and with sodium N-benzyl-D-glucamine-N-carbodithioate (BGDTC) was evaluated in albino rats. They received 109Cd intraperitoneally once and 1 week later chelation therapy six times over 12 days at 2-day intervals. The treatment groups were: 1, control; 2, BGDTC six times; 3, C9G2DTC six times; 4, C9G2DTC three times followed by BGDTC three times; 5, C9G2DTC twice followed by BGDTC four times; 6, C9G2DTC once followed by BGDTC five times. The radioactivity in liver, kidney and brain was determined 19 days after 109Cd administration. Results were expressed as a percentage of the 109Cd dose and differences were analyzed by Duncan's multiple range test (P < 0.05). Treatment with C9G2DTC resulted in higher Cd reduction in the liver and lower in the kidney than with BGDTC, which is in agreement with our previous findings. Combined treatment resulted in a greater reduction of Cd in the liver and kidney than by using either chelating agent alone, irrespective of the number of C9G2DTC or BGDTC treatments, and without causing redistribution to the brain. The important aspect of this work is that C9G2DTC--the novel cadmium chelating agent which is extremely efficient in reducing Cd liver deposits and about three times more toxic than BGDTC--has to be used only once at the beginning of the treatment to obtain optimal reduction of aged organ cadmium deposits.
Animals↗
Racemic-2,3-dimercaptosuccinic acid for inorganic mercury mobilization in rats.
The efficiency of racemic-2,3-dimercaptosuccinic acid (rac-DMSA) compared with meso-2,3-dimercaptosuccinic acid (meso-DMSA) in mobilizing inorganic mercury was evaluated in female rats. Chelators were administered orally at a dose of 0.5, 1.0 or 2.0 mmol kg-1 on four consecutive days, 5 days after a single intraperitoneal 203Hg injection (with 0.5 mg HgCl2 kg-1). Both chelators reduced 203Hg retention in whole body and kidney and at higher doses also in the liver. Racemic-DMSA was more efficient at lower dose levels and equal to meso-DMSA at the highest dose level. Kidney retention decreased after rac-DMSA to 27, 10 and 10% of controls and after meso-DMSA to 68, 39 and 10% of control values at the 0.5, 1.0 and 2.0 mmol kg-1 dose level, respectively. Since meso-DMSA is already approved for human use, its stereoisomeric form, rac-DMSA, deserves further attention for treatment of mercury poisoning.
Administration, Oral↗
Combined chelation therapy in reducing tissue lead concentrations in suckling rats.
The very young are more prone to lead poisoning than adults, and the treatment with chelating agents, either as monotherapy or combined treatment, is still a matter of dispute. The purpose of this work was to evaluate the efficiency of three chelating agents administered either as monotherapies or as combined treatments in sucklings. Lead acetate (5 mg Pb kg(-1) i.p.) was administered to the 7-day-old rat pups in eight litters on experimental day 1 and chelating agents on experimental days 2 and 3. Pups were divided into six groups: (1) untreated control; (2) EDTA (calcium disodium ethylendiaminetetraacetate, 0.3 mmol kg(-1) i.p. at 4 p.m.); (3) meso-DMSA (meso-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (4) rac-DMSA (racemic-2,3-dimeracaptosuccinic acid, 0.5 mmol kg(-1) p.o. at 10 a.m.); (5) EDTA+meso-DMSA; and (6) EDTA+rac-DMSA. Rats were killed on experimental day 5. Tissue element concentrations were analyzed by atomic absorption spectrometry. Treatment with EDTA did not affect tissue Pb, but it reduced Zn in the carcass and liver. Meso-DMSA reduced Pb in the kidneys and brain, and it did not affect organ essential elements. Rac-DMSA most efficiently reduced Pb concentrations in the carcass, kidneys and brain, but it also reduced Zn and Cu in the liver and Zn in the kidneys. Combined treatments with EDTA never improved the efficiency of either DMSA isoform in decreasing tissue Pb but they did reduce tissue Zn concentrations. All treatments caused the same decrease in the carcass Ca concentrations. The results do not support combined treatment in this age group, which is especially sensitive to trace element deficiencies, and suggest that meso-DMSA might be the treatment of choice in acute lead poisoning in infants.
Animals↗
Organ cadmium deposits in orally exposed female rats and their pups and the depleting efficiency of sodium N-(4-methoxybenzyl)-D-glucamine-N-carbodithioate monohydrate (MeOBDCG).
Cadmium was given to female rats in the drinking water (50 ppm Cd) from 4 weeks before mating until weaning (a total of 10 weeks). Four weeks after the discontinuation of exposure, mothers and offspring were then given two i.p. doses of 1 mmol kg-1 sodium N-(4-methoxybenzyl)-D-glucamine-N-carbodithioate monohydrate (MeOBDCG) on subsequent days. Cadmium in kidneys and liver was determined in groups of mothers before mating and in mothers and pups after parturition, at the end of lactation and 4 and 5 weeks after the discontinuation of exposure. An additional measurement was made in pups in the middle of the lactation period. Cadmium deposition rapidly increased in the two organs between the 11th and 21st day of lactation. At all times, Cd concentrations in the liver and kidneys of mothers were several orders higher than in the offspring. After the discontinuation of exposure, maternal hepatic and renal Cd contents showed a significant decrease. Treatment with the chelator depleted the hepatic Cd stores in mothers by 90% and in pups by 80%, while the corresponding renal depletions were only 23% and 12%, respectively. The liver and kidney contents of Cd (but not the concentration) increased by a higher factor during lactation than during pregnancy and exposure during lactation was also more important for pups than prenatal exposure. The lower efficiency of the chelator in the offspring indicates that Cd accumulated during the neonatal period was less accessible to treatment with chelating agents than Cd accumulated in later life.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Decreasing 203Hg retention by intraperitoneal treatment with monoalkyl esters of meso-2,3-dimercaptosuccinic acid in rats.
The effect of nine monoalkyl esters of meso-2,3-dimercaptosuccinic acid (DMSA) on 203Hg retention after a single i.p. dose was evaluated in 6-7 week-old female albino rats. The monoesters were the monomethyl (MMDMS), monoethyl (MEDMS), mono-n-propyl (Mn-PDMS), monoisopropyl (Mi-PDMS), mono-n-butyl (Mn-BDMS), monoisobutyl (Mi-BDMS), mono-n-amyl (Mn-ADMS), monoisoamyl (Mi-ADMS) and mono-n-hexyl (Mn-HDMS). Dimercaptosuccinic acid or one of the monoesters were administered at a dose of 0.25 mmol kg-1 body wt. twice, i.e. 30 min and 24 h after 203Hg administration. The whole body (WB) radioactivity was determined on the 2nd, 4th and 6th days. The radioactivity in the carcass (C) (whole body without the gastrointestinal tract), liver (L), both kidneys (K) and brain (B) was determined 6 days after 203Hg administration. All treated animals had a significantly lower body burden of mercury than the controls. The reduction of 203Hg retention in WB and other body compartments was higher in animals treated with monoesters than in rats treated with DMSA. The relative effectiveness of the monoesters was dependent on the nature of the alkyl groups, the efficiency being higher in higher analogues. Maximum activity was attained with the C5 (Mn-ADMS, Mi-ADMS) and C6 (Mn-HDMS) esters. These chelators reduced WB, C, L, K and B mercury retention by 90, 89, 76, 93 and 80%, respectively. Iso derivatives were more efficient than the normal isomers (Mi-PDMS > Mn-PDMS; Mi-BDMS > Mn-BDMS; Mi-ADMS > Mn-ADMS).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Monoisoamyl and mono-n-hexyl meso-2,3-dimercaptosuccinate in mobilizing 203Hg retention in relation to age of rats and route of administration.
Monoisoamyl (Mi-ADMS) and mono-n-hexyl (Mn-HDMS) monoesters of meso-2,3-dimercaptosuccinic acid (DMSA) were given orally or parenterally for the mobilization of inorganic mercury in suckling and older rats. Chelators were administered at a dose of 2 x 0.5 mmol kg-1 on two consecutive days 2 weeks after a single 203Hg injection. Six days later, whole-body, kidney, liver and brain radioactivities were determined in gamma scintillation counters. Both Mi-ADMS and Mn-HDMS were found to be superior to DMSA in mobilizing mercury from body and organs. The results were similar after oral or parenteral treatment. The efficiency of both monoesters was even higher in younger than in older rats. This is the first report on the mobilization of mercury from the body of sucklings under conditions of late oral treatment.
Administration, Oral↗
Succimer treatment during ongoing lead exposure reduces tissue lead in suckling rats.
There is a concern that oral treatment with succimer (meso-2, 3-dimercaptosuccinic acid, DMSA) can promote gastrointestinal lead absorption if not performed in a lead-safe environment. The scope of our investigation was to evaluate the efficacy of oral DMSA treatment during oral lead exposure on tissue lead in suckling rats. Six-day-old Wistar rats of both genders were divided into two groups-untreated (Pb) and treated (Pb + DMSA)-with 10 animals per group. Lead (as acetate) was given orally at a dose of 2 mg kg(-1) body weight day(-1) for eight consecutive days (total dose 16 mg kg(-1), i.e. 0.08 mmol kg(-1)). During this period the treated group received a daily dose of 0.5 mmol DMSA kg(-1) body weight p.o. six times on days 1-3 and 6-8 of the experiment (total dose 3 mmol kg(-1)). Tissue lead was determined by means of atomic absorption spectrometry. The DMSA efficiently reduced the lead concentration in the analysed tissues (carcass, liver, kidneys and brain) by approximately 50% compared with untreated controls. The pups' growth and organ weights were not affected. In conclusion, our results indicate that DMSA is an efficient oral lead chelator in sucklings even if challenged with ongoing lead exposure.
Animals↗
Carbodithioate MeOBDCG for decreasing intracellular cadmium deposits in rats of different ages.
The efficiency of chelating agents to remove aged intracellular deposits of cadmium in young and older rats was studied. The administration of the chelating agent sodium N-(4-methoxybenzyl)-D-glucamine-N-carbodithioate monohydrate (MeOBDCG) 2 wk after a single intraperitoneal 115m Cd administration reduced the whole body, liver, and kidney retention in suckling rats to about 63, 42, and 71 percent and in older rats to 39, 17, and 76 percent of values obtained in respective controls. Chelation therapy was generally more effective in older than younger rats and the age-related effect was most pronounced in the liver. These results indicate that specific features of young organisms may significantly alter the effect of chelation treatment.
Aging↗
Interaction of lead with some essential elements in rat's kidney in relation to age.
The aim of this study was to evaluate the interaction of lead given orally with Fe, Zn, and Cu in adult female rats and in their pups. Kidney was chosen for studying this interaction. Four different doses of lead (acetate) from 1500 to 7500 ppm were administered to mature female albino rats in beverages during 6 wk. The exposure lasted from mating up to 3 wk after delivery. Pb, Fe, Zn, and Cu were determined in kidneys of mothers and pups. Histopathological examinations were also performed. Results showed significantly lower concentrations of Fe, Zn, and Cu in kidneys of mothers on all lead levels. Their pups showed no change in concentrations of essential elements and even increased Fe at the highest exposure level. Concentrations of Pb and histopathological changes in the kidney were similar in mothers and offspring, although pups received only a fraction of the mothers' doses. Our results indicate that in immature animals the interaction of Pb with essential elements in the kidney is different from that in their mothers.
Aging↗
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. Radionuclides 115mCd, 203Hg, and 141Ce were administered orally to 6-d-old rats. Chelating agent Zn-DTPA (3.64 mmol/kg) was administered to animals that received 115mCd or 141Ce and Na-DMPS (375 mumols/kg) to those that received 203Hg, immediately and 24 h or 24 and 48 h after radionuclide administration. Radioactivity 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.
Animals↗
Placental cadmium and progesterone concentrations in cigarette smokers.
Cadmium and progesterone concentrations were evaluated in term placentas collected from 56 healthy parturients in the city of Zagreb. Concentrations of lead, iron, zinc, and copper in placentas were analyzed. Data collected by questionnaire identified 29 nonsmoking and 27 smoking women. From each placenta, three samples from different locations were taken. Metals were measured by atomic absorption spectrometry. Progesterone was determined by specific radioimmunoassay in homogenized and lyophilized tissue samples after steroid extraction with ethanol. No effect of sample location was found. In placentas of smoking women an increase in cadmium, reduced progesterone and a decrease in iron concentrations were found. Placental copper and zinc concentrations were not altered. In conclusion, the results present new evidence that maternal smoking reduces placental progesterone content and support the established association of smoking with placental cadmium.
Adult↗
Molecular-modeling design of cadmium-mobilizing agents: a novel biscarbodithioate.
This report describes the design, synthesis, characterization, and in vivo cadmium-mobilizing properties of a novel biscarbodithioate chelating agent, namely, disodium N,N'-diglucosyl-1,9-nonanediamine-N,N'-biscarbodithioate+ ++ (C9G2DTC), HOCH2(CHOH)4CH2(CS2Na)N(CH2)9N(CS2-Na)CH2( CHOH)4CH2OH, which can coordinate to a single cadmium ion with both of its carbodithioate groups (CS2Na) in its folded configuration. When evaluated for its cadmium efficacy at 1.0 mmol/kg x 5 ip in 109Cd-pretreated rats against sodium N-benzyl-D-glucamine-N-carbodithioate (BGDTC) as standard, the biscarbodithioate was found to reduce the whole-body levels of cadmium more rapidly in the rat than BGDTC which contains only one CS2Na group. The whole-body Cd depletions after the first ip injection of the new and the standard compound were 52% and 23%, respectively. The C9G2DTC was found to be more effective in removing cadmium from the liver (% Cd reductions compared to controls: C9G2DTC, 94, and BGDTC, 85), but slightly less effective in reducing renal cadmium levels (% Cd-reductions: C9G2DTC, 44, and BGDTC, 60). The ip LD50 of the bis-DTC was estimated to be slightly in excess of ca. 4.0 mmol/kg in the rat. A molecular model of this chelating agent indicates that, because of the flexibility of the nonane chain, both carbodithioate groups can approach closely enough to each other to permit complexation with the same cadmium ion to give a resulting structure without significant strain. A mechanism for the removal of Cd from CdMT by C9G2DTC is also proposed.
Animals↗
In vivo cadmium mobilization by three novel bis(carbodithioates).
Four novel cadmium-chelating agents N,N'di(D-glucosyl)alkanediamine-N,N'-bis(carbodithioates) 4a-e were prepared as disodium salts of the general formula (CH2)n[N(CS2Na)CH2(CHOH)4CH2OH]2, where n = 7, 8, 10, and 12. They were synthesized by the reductive coupling of 2 mol of alpha-D-(+)-glucose (1) with 1 mol of the corresponding alkanediamines 2a-e followed by reaction with CS2 in a basic medium. The elemental analyses of the Cd complexes 5a, b, d, and e prepared revealed that these bis(carbodithioates) form 1:1 complexes with Cd2+. The in vivo cadmium-mobilizing efficacy of three of the new chelators (4a, b, and d) was determined in rats pretreated ip with CdCl2.H2O containing 2 microCi of 109Cd (74 kBq), and comparable data were obtained on a previously reported member of this series (4c, n = 9), and with BGDTC (sodium N-benzyl-D-glucamine-N-carbodithioate, 6), all given once at 1.0 mmol/kg ip. The compound with n = 12 (4e, C12G2DTC) proved to be too toxic in the preliminary study and was not evaluated further. A single injection of the 4a, b, and d caused a reduction in Cd levels of the whole body to ca. 50% and liver to ca. 12% of control levels. Comparable experimental data on BGDTC resulted in a reduction of whole-body cadmium to only 78% of the control levels and a reduction in liver cadmium to only 56% of control. After one and six injections at the same dosage, the new chelators (4a, b, and d) and C9G2DTC (4c, n = 9) significantly surpassed BGDTC for whole-body and liver Cd depletion but caused only a very modest depletion of renal Cd. While these compounds were designed to allow the two dithiocarbamate groups to coordinate to the same Cd2+ in vivo, the data do not prove that the two > NCS2Na groups bind to the same cadmium ion in vivo. The very rapid reduction in liver cadmium levels following only a single injection indicates that these -2 anions rapidly gain access to intracellular hepatic sites by some transport system.
Animals↗
Influence of sex and dietary calcium on intestinal cadmium absorption in rats.
The influence of sex and dietary calcium on whole-body retention of orally administered 115mCdCl2 has a half-life of 43 days, distinguishing it from 115Cd of half-life 2.3 days was studied in one-year-old control and gonadectomized male and female rats. Gonadectomy was performed at the age of four months. Each of the four experimental groups was divided into three subgroups that were fed rat food with a different calcium content (2.4, 0.7, and 0.3% Ca) throughout the experiment. Regardless of sex and gonadectomy the mean percent values of 115mCd retention in the whole body decreased with increasing dietary calcium level. Male rats retained less cadmium than all other experimental groups of animals. These data clearly point out that sex and diet might influence the level of ingested cadmium in the body.
Animals↗