Cadmium In Rats Research Articles

Comparison of effectiveness of 3 dithiocarbamates on excretion and distribution of cadmium in rats and mice

Sodium N- benzyl- D - glucamine dithiocarbamate (BGD), sodium N-p- methylbenzyl- D - glucamine dithiocarbamate (MBGD), and sodium N-p- isopropylbenzyl- D - glucamine dithiocarbamate (PBGD), which were recently synthesized, were evaluated for their efficacy in the distribution and excretion of cadmium in rats and mice exposed to cadmium. Rats and mice were injected i.p. with 109CdCl 2 (1 mg Cd/kg and 2 μCi 109Cd/one animal) and 3 days later, they were treated with the dithiocarbamates (400 μmol/kg) every other day for 2 weeks. These dithiocarbamates were effective in removing cadmium from the body without increasing the cadmium content in the kidney. After treatment with BGD, MBGD, and PBGD, cadmium was excreted mainly in the feces and the effect of MBGD and PBGD on the fecal excretion of cadmium was much larger than that of BGD. The treatment with these dithiocarbamates did not cause the redistribution of cadmium to brain, testes, and heart in rats and mice. The treatment of mice with PBGD decreased the concentrations of essential metals in liver, kidney, and brain. The extent of acute toxicity of the dithiocarbamates in mice was in the order PBGD > MBGD > BGD.

Change in Renal Copper, Zinc-Metallothionein Concentration with Pregnancy and Effect of Preloaded Cadmium in Rats (Regular Presentations) (Proceedings of the 15 th Symposium on Environmental Pollutants and Toxicology)

Change in Renal Copper, Zinc-Metallothionein Concentration with Pregnancy and Effect of Preloaded Cadmium in Rats (Regular Presentations) (Proceedings of the 15 th Symposium on Environmental Pollutants and Toxicology)

In vivo and in vitro medical diagnoses of toxic cadmium in rats

Rat exposed to toxic cadmium chronically and acutely are diagnosed byin vivo promt gamma-ray activation andin vitro neutron activation using nuclear reactor neutron beam. Linear correlation of bothin vivo andin vitro methods is established, damage level of 1.7 mg/g Cd in kidneys and 0.16 mg/g Cd in liver are confirmed by biochemical diagnosis. Features ofin vivo andin vitro nuclear medical diagnoses of cadmium contamination, serving as the basis for future research and correletion to human beings, are discussed.

Effect of N-benzyl- d-glucamine dithiocarbamate on the renal toxicity produced by subacute exposure to cadmium in rats

The effect of N-benzyl- d-glucamine dithiocarbamate (BGD) on the renal toxicity produced by subacute exposure to cadmium in rats was studied. Rats were injected sc with CdCl 2 (1.5 mg Cd/kg) daily for 26 days and thereafter they received 13 injections of BGD (400 μmol/kg) every other day. Urinary protein concentration and AST activity significantly increased after 20 days of cadmium treatment. The pattern of the increase in the urinary excretion of cadmium after cadmium treatment was consistent with that in the urinary excretion of protein and AST. Urinary excretion of amino acid increased gradually after the cessation of cadmium treatment. BGD treatment significantly decreased the urinary excretion of protein, aspartate aminotransferase (AST), and amino acid. Plasma AST activity was elevated 8 days after the beginning of cadmium treatment, indicating that the hepatic damage occurred prior to the renal damage. In addition, the microscopic examination of renal tissue from cadmium-treated rats revealed the necrosis of the proximal tubular cells. The cadmium concentrations in liver and kidney were significantly decreased by BGD treatment. The results of this study indicate that BGD treatment is effective in decreasing the cadmium concentrations in liver and kidney, resulting in the therapeutic effect on the cadmium-induced renal damage.

Effect of Ethanol on the Excretion of Cadmium in Rats (Proceedings of the 14th Symposium on Environmental Pollutants and Toxicology)

Effect of Ethanol on the Excretion of Cadmium in Rats (Proceedings of the 14th Symposium on Environmental Pollutants and Toxicology)

Subcellular toxicity of low level cadmium in rats: Effect on cytochrome c oxidase

The in vivo effect of cadmium (Cd) with or without prior administration of L-cysteine (Cys) or diethylmaleate (DEM) on hepatic and renal cytochrome c oxidase (Cyt- c-Ox), essential metals and mitochondrial thiols was investigated. Male Sprague—Dawley rats were given 25 μg Cd/kg (as Cd acetate) orally 5 times a week for 6 weeks. Different groups of animals additionally received either Cys (500 mg/kg per day, p.o.) or DEM (0.85 mg/kg, i.p.) by multiple administration. Parameters were determined 1 day after the last gavage. Cadmium decreased the activity of Cyt- c-Ox in mitochondria of livers but not in those of kidneys. Copper in both tissue and mitochondria were unaffected whereas hepatic tissue iron decreased by 50% upon Cd gavage. Cysteine pretreatment increased hepatic and especially renal mitochondrial Cd, but diminished the Cd effect on Cyt- c-Ox and increased hepatic tissue iron. Both DEM and DEM/Cd treatment decreased Cyt- c-Ox by 50% in liver but not in kidneys. Metallothionein was not significantly altered by either treatment. Considering data from all the experimental groups Cyt- c-Ox activity seems to be related rather to the amount of protein thiols than to either copper or iron in hepatic mitochondria. The data demonstrate the high susceptibility of hepatic vs. renal mitochondria and suggest the involvement of thiols in Cyt- c-Ox activity.

Effects of low-level cadmium in rats: Influence of pretreatment with thiol-modulating agents

The effects of low-level cadmium (Cd) administration to rats on animal health, liver and kidney thiols, metallothionein, and glutathione reductase (GSSG reductase) and their modulation by cysteine (as a possible protector) and diethyl maleate (as a possible potentiator) have been investigated. Male Sprague-Dawley rats were treated with sodium or Cd acetate (25 micrograms Cd/kg) orally five times a week for 6 weeks. A second group of animals received cysteine (500 mg/kg; po) before each gavage while a third group received diethyl maleate (DEM) (0.85 mg/kg; ip) in addition to sodium or Cd acetate. When rats were treated with cadmium alone neither weight gain nor serum parameters indicative of hepato- or nephro-toxicity were affected. However, acid-soluble thiols, primarily glutathione, were decreased by about 25% in liver only. A tendency to a decrease in hepatic protein thiols was also noted. No changes were observed for hepatic or renal metallothionein in response to this low level of cadmium administration alone or in combination with the other treatments. Animals receiving cysteine, either alone or with cadmium, showed decreased body weight gain, but no change in serum parameters. Acid-soluble thiols in liver were lower in cysteine-treated rats (24%) and cysteine + Cd (33%) while kidney thiols were unaffected. Administration of DEM alone or with Cd did not cause any alteration in body weight gain. When given DEM + Cd, however, an increase in serum bilirubin was observed, which suggests interference with hepatobiliary function. Acid-soluble thiols were decreased by DEM alone (45%) and DEM + Cd (51%) in liver while renal thiols showed no change. Our data indicate that low-level Cd gavage decreases hepatic cellular thiols but not those of kidney. Cysteine gavage does not protect from the Cd-related effect. Indeed, cysteine itself was found to reduce acid-soluble thiols under the experimental conditions. This was observed only in liver, as was the decrease in thiols due to DEM treatment. DEM administration together with Cd resulted in signs of liver toxicity. There is no indication that inhibition of GSSG reductase by Cd might be involved in the thiol-decreasing effect of short-term repeated low-level gavage of Cd to rats.

Mitochondrial effects of low-level cadmium in rats: interaction with zinc.

Male Sprague-Dawley rats were treated with sodium or cadmium (Cd) 4 acetate (25 μg Cd per kg body weight) orally 5 times a week for 6 weeks. A second group of animals was repeatedly injected with zinc sulphate (6 and 12 mg zinc (Zn) per kg ip) with or without Cd gavage. Cadmium treatment alone yielded no obvious toxic effects as evidenced by serum constituents or animal weight gain. Similarly, Zn injection did not affect these criteria. Zinc injection increased metallothionein in liver and kidneys and increased renal Cd. Cytosolic sorbitol dehydrogenase was not influenced by either cadmium, Zn or Cd + Zn exposure. However, individual Cd gavage decreased mitchochondrial cytochrome c oxidase in liver by 50%. This was partly protected by Zn. Hepatic adenosine triphosphatase (ATPase) was not affected by any of the treatment regimens. However, renal ATPase was inhibited by combined Cd + Zn administration. The data suggest subcellular toxic effects due to treatment with low Cd doses as evidenced by the decrease in hepatic cytochrome c oxidase. Simultaneous Zn injection may reduce this effect of Cd in liver. However, the treatment of rats by low level Cd gavage combined with zinc administration impairs the animals' health as shown by weight loss.

Long term lung clearance and cellular retention of cadmium in rats and monkeys

Results of both experimental animal studies and of epidemiologieal studies have shown that chronically inhaled cadmium compounds can have deleterious effects. Lung emphysema, lung fibrosis, chronic bronchitis, lung tumors and also renal dysfunction have been described (Friberg et al, 1974; Holden, 1980; Takenaka et al, 1983; Thun et al, 1985). Most of the experimental animal studies have been performed in rats, and the cadmium compound used was mostly CdCI 9. A more relevant compound for occupational human exposure, however, is Cd0. Thus,'when attempting to extrapolate results from rat inhalation studies with CdCI 9 to humans the question of the validity of such attempts arises. For example, we%ave found that CdCI 9 inhaled at low concentrations induces primary lung tumors in rats (Takenaka et ~i, 1983) yet epidemiological evidence in Cd exposed human workers seems to indicate a lower sensitivity of humans towards the pulmonary carcinogenic effect of inhaled Cd.

The effect of wheat bran on the absorption and accumulation of cadmium in rats.

1. The major purpose of the present study was to determine whether the addition of wheat bran to endosperm crisp bread in a composite diet given to rats for 6 weeks causes an increase in the accumulation of cadmium in the rats due to the Cd content in the bran, or whether binding factors in the bran, such as dietary fibre and phytic acid, reduce or prevent the accumulation of this Cd. A second purpose was to determine whether the accumulation of Cd can be estimated by measuring the absorption of 109Cd given in a single meal of the diet. 2. Three groups of eight rats were fed on one of three diets. Half of each diet consisted of a basal mixture of starch, protein, oil, minerals and vitamins. The remainder consisted of crisp breads based on refined wheat flour (endosperm group), wheat flour + bran in equal amounts (bran group) and wheat flour + Cd to give a Cd content similar to that of the bran group (endosperm + Cd group). After 41 d on the diets, the rats were deprived of food but not water for 12 h and then given a 5 g test meal of their respective diets with 109Cd added. After 3 h the remaining 109Cd-labelled diets were replaced with the unlabelled diets for 3 h before the rats were killed. 3. The total Cd contents in the wall of the proximal small intestine, including mucus, and in the liver and kidneys were highest in the endosperm + Cd group and lowest in the endosperm group.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of several chelating agents on the distribution and binding of cadmium in rats.

Male Sprague-Dawley rats were injected with 109CdCl2 (3 mumol Cd/kg) and killed between 1 h and 200 d afterwards. Metal concentration in the critical organs, i.e. liver and kidneys decreased very slowly. Within the cells Cd is found mainly in the cytosol and--at very early times--in the nuclei. Within the cytosol of the liver most of the metal is initially bound to proteins with high molecular weight but as early as 3 h after incorporation more than 90% is bound to metallothionein which is always the main binding site in the kidneys. Of the chelating agents tested only BAL and Puchel were able to reduce the body burden significantly. Both are lipophilic substances. Puchel cannot reduce the kidney Cd burden but removes Cd from the liver only while BAL is effective in both organs. Both chelating agents exert their effects at doses which are too near to the LD50 to be considered as safe enough for human use.

Effect of co-exposure to ethanol and cadmium in rats.

Metabolism and toxicity of heavy metals may be influenced by certain factors such as protein malnutrition, essential element deficiency or alcoholism. Ethanol has been found to enhance the absorption of lead in body and alcoholics have been reported to be more susceptible to lead intoxication. As alcoholism may be common among industry workers and a significant section of population, who may be exposed to cadmium, it was considered of interest to investigate the influence of ethanol-cadmium co-exposure on cadmium sensitive hepatic, renal and serum enzymes, tissue accumulation of cadmium, essential trace element status and cadmium induced hepatic metallothione in synthesis in rats.

Studies on the influence of calcium on cadmium absorbed by rat liver and the resistivity against the toxicity of cadmium in rat.

There have been reports on the effect of Ca on the uptake of Cd. A low dietary uptake of Ca can result in an increasing accumulation of Cd in the kidney and can increase the susceptibility to the deleterious effects of environmental Cd. However, up to now, there have been no reports on what role Ca plays in the uptake of Cd after supplementary Ca is added to the diet. One of the purposes of this work was to compare the amount of Cd in the livers of rats which were fed by rations containing various amounts of supplementary Ca (Ca-Cd test in brief). In addition, we determined the intestinal absorption of Ca, using drinking water containing 100 ppm Cd to feed the rats for seventeen days (Cd treatment in brief) and then in vitro determined the absorption capability of Cd in the duodenum.

Effect of N-benzyl-d-glucamine dithiocarbamate on distribution and excretion of cadmium in rats

The effect of sodium N-benzyl-D-glucamine dithiocarbamate (NBG-DTC) on the distribution and excretion of cadmium in rats exposed to cadmium and the chemical form and intestinal reabsorption of cadmium compound excreted in the bile were studied. Rats were injected intraperitoneally with 109CdCl 2 (1 mg Cd and 10 μCi 109Cd/Kg) and 24 h later, they were injected with NBG-DTC (400 or 1200 μmol/kg). The biliary excretion of cadmium was remarkably increased by intraperitoneally injection of NBG-DTC, while there was only a small increase in urinary excretion of cadmium. Such an enhancement effect of NBG-DTC on the biliary excretion of cadmium was much larger at the high dose (1200 μmol/kg) of NBG-DTC. The treatment with NBG-DTC significantly decreased the cadmium content in the liver at the dose of 1200 μmol/kg and did not result in the undesirable redistribution of cadmium to the tissues, such as brain, testes, heart and lung. In addition, it was found that the cadmium compound excreted in the bile was mainly characterized as cadmium-NBG-DTC and which was not reabsorbed from the intestinal tracts.

Studies on poisonous metals. XVIII. Effects of several dithiocarbamates on tissue distribution and excretion of cadmium in rats.

The effects of various chelating agents, sodium N-benzyl-D-glucamine dithiocarbamate (NBGDTC), sodium N-p-methylbenzyl-D-glucamine dithiocarbamate (NMBGDTC), and sodium N-p-isopropylbenzyl-D-glucamine dithiocarbamate (NPBGDTC), which were newly synthesized, sodium N-methyl-D-glucamine dithiocarbamate (NMGDTC), diethyldithiocarbamate (DEDTC), dihydroxyethyldithiocarbamate (DHEDTC), and dicarboxymethyldithiocarbamate (DCMDTC), on the distribution and excretion of cadmium in rats were compared at 30 min and 24 h following cadmium injection. At 30 min after cadmium administration, these chelating agents all significantly enhanced the biliary excretion of cadmium, and at 24 h after cadmium injection, the chelating agents other than DEDTC and DCMDTC significantly enhanced the biliary excretion of the metal. The effects of NBGDTC, NMBGDTC, and NPBGDTC on the biliary excretion of cadmium were much larger than those of the other chelating agents. The urinary excretion of cadmium was increased by the chelating agents other than DEDTC and NPBGDTC. These chelating agents were effective in mobilizing cadmium from the liver, kidney, and pancreas at 30 min after treatment with cadmium. At both 30 min and 24 h after treatment with cadmium, NBGDTC, NMBGDTC, and NPBGDTC effectively depressed cadmium content in the liver without the mobilization of cadmium to the kidney. The chelating agents other than DEDTC did not result in the redistribution of cadmium to the brain, testes, lung, and heart. These results show that the injection of NBGDTC, NMBGDTC, or NPBGDTC at both 30 min and 24 h after treatment with cadmium can much more effectively mobilize cadmium from the body, mainly through the bile, without redistribution of cadmium to other tissues, such as brain, testes, lung, and heart, when compared with injection of other chelating agents. Furthermore, the pattern of mobilization and excretion of cadmium following treatment with each chelating agent was related to the organic/aqueous partition coefficient of each dithiocarbamate-cadmium complex.

The effect of wheat bran on the excretion of cadmium in rats.

The influence of wheat bran as a source of dietary fibre on the excretion of ingested cadmium from diet was studied. The cadmium contents in the diets, faeces, urine, liver, kidney and spleen were determined, as well as the weight gains, the relative weights of the cited organs, and the levels of alkaline phosphatase in serum. No evidence is provided that an increasing portion of wheat bran in the diets induced an increase in cadmium excretion. Changes in the studied toxicity parameters were not found.

Effects of chelating agents on biliary and urinary excretion and tissue distribution of cadmium in rats

Sodium N- benzyl- d-glucamine dithiocarbamate (NBG-DTC), which was newly synthesized, sodium N- methyl- d-glucamine dithiocarbamate (NMG-DTC), and 2,3-dimercapto-1-propanol (BAL) were evaluated for their efficacy in mobilization of cadmium from the body using rats which had received cadmium, 30 min and 24 h earlier. At both 30 min and 24 h after treatment with cadmium, these chelating agents significantly enhanced the biliary excretion of cadmium, but did not influence the urinary excretion of the metal. Such an enhancement effect of NBG-DTC on the biliary excretion of cadmium was much larger than that of NMG-DTC or BAL. These chelating agents were effective in mobilizing cadmium from the liver at 30 min after pretreatment with cadmium. NBG-DTC showed the largest effectiveness on the depression of cadmium content in the liver. However, the contents of cadmium in the liver and kidney of rats given cadmium, 24 h earlier, did not significantly change at 3 h after treatment with the chelating agents. These results show that the injection of NBG-DTC at both 30 min and 24 h after treatment with cadmium can much more effectively mobilize cadmium from the body mainly through the bile without redistribution of cadmium to tissues than injection of NMG-DTC and BAL.

Influence of manganese on the gastrointestinal absorption of cadmium in rats.

Four groups of male rats were given the following oral treatment: control group (n = 20) deionized drinking water, Mn group (n = 20) deionized drinking water containing 56 ppm Mn2+ (1 mmol/l), Cd group (n = 10) deionized drinking water containing 112 ppm Cd2+ (1 mmol/l) and Cd + Mn group (n = 10) deionized drinking water containing 112 ppm Cd2+ and 56 ppm Mn2+. Half of each group was sacrificed after 4 weeks and the other half after 8 weeks of treatment. At each time interval, the mean levels of Mn in blood, in urine and in the various tissues did not differ between the control and Mn groups. Furthermore, comparable Mn levels were found after 4 and 8 weeks of treatment. Microscopical examination of the brain failed to reveal any overt morphological alteration in the Mn group. With respect to the control group, the Cd and Cd + Mn groups exhibited increased levels of Cd in blood, urine, liver, whole kidney, kidney cortex and in brain (cortex, cerebellum, basal ganglia), but the Cd + Mn groups showed invariably lower levels than the Cd group after 4 weeks as well as after 8 weeks. These results suggest that the rate of gastrointestinal absorption of Cd is decreased by supplementation of the drinking water with a 'non-toxic' dose of Mn2+.

Comparative effects of three chelating agents on distribution and excretion of cadmium in rats

Sodium N-benzyl- d-glucamine dithiocarbamate (NBG-DTC), which was newly synthesized, 2,3-dimercaptopropanol (BAL), and N-methyl- d-glucamine dithiocarbamate (NMG-DTC) were compared for their relative efficacies in the distribution and excretion of cadmium in rats exposed to cadmium. Rats were injected ip with 109CdCl 2 (1 mg Cd and 10 μCi 109Cd/kg) and 3 days later, they were treated with the chelating agents (400 μmol/kg) every other day for 2 weeks. These chelating agents were effective in removing cadmium from the body without increasing the amount of cadmium in the kidney. After treatment with these chelating agents, cadmium was excreted mainly in the feces through the bile and the fecal excretion of cadmium by NBG-DTC was significantly larger than that by BAL or NMG-DTC. The hepatic cadmium content after treatment with NBG-DTC was much more decreased than that with BAL or NMG-DTC. The renal cadmium content was decreased only after treatment with NBG-DTC. These chelating agents did not result in the redistribution of cadmium to brain, testes, and heart. The growth of rats was little retarded by treatment with NBG-DTC and NMG-DTC, but was retarded by treatment with BAL. The treatment with NBG-DTC decreased the tissue amounts of Zn, Fe, and Mn to a small extent as compared with the treatment with cadmium alone. The results of this study reveal that the injection of NBG-DTC to rats pretreated with cadmium can more effectively remove cadmium from the body without the mobilization of cadmium to the kidney, the critical organ in cadmium toxicity, and without redistribution of cadmium to other tissues such as brain, testes, and heart, than injection of BAL and NMG-DTC.

Studies on poisonous metals. XVI Effects of chelating agents on inhibition of L-histidine absorption with cadmium in rats.

The effects of chelating agents, such as citric acid, ethylendediaminetetraacetic acid (EDTA), L-cysteine and L-leucine, on the inhibition of small intestinal absorption of L-histidine with cadmium in rats were studied. The depressed absorption of L-histidine (1.29 mM) from the small intestine of rats in situ in the presence of cadmium (0.27 mM) was greately restored by the addition of citric acid (10-20 mM) and EDTA (0.5 mM), and moderately by L-cysteine (1.29 mM). In addition, the intestinal accumulation of cadmium was significantly decreased by the addition of citric acid, EDTA and L-cysteine. An in vitro intestinal experiment suggested that the result of complexing of cadmium by the chelating agents, such as citric acid, EDTA and L-cysteine, decreased the accumulation of cadmium in the intestinal tissue and protected the active transport of L-histidine across the rat small intestine.