Cadmium-treated Group Research Articles

Possible role of oxidative stress in acute cadmium hepatotoxicity in rats

It is known that cadmium induces a variety of functional disorders, especially liver and kidney dysfunction. The main mechanism involved in cadmium hepatotoxicity is its binding to sulfhydryl groups and initiation of inflammation. Additionally, oxidative stress, due to a decrease in antioxidative capacity, plays a role in chronic cadmium hepatotoxicity. The role of oxidative stress in acute cadmium intoxication is still not clear. The aim of our study was to investigate the role of reactive oxygen species and efficiency of antioxidant protection in rat liver in acute cadmium intoxication. Male Wistar rats (n=16) were divided into the following groups: 1. control group (n=7), treated with saline, 2. cadmium-treated (n=9) with a single dose of 2.5 mg/kg intraperitoneally. After administration (24 hours), blood samples from the right side of the heart and liver samples were collected for the determination of oxidative stress parameters. In our study malondialdehyde concentration was elevated both in plasma and liver after cadmium administration (p<0.01). Moreover, superoxide dismutase activity was increased in the cadmium-treated group, mainly due to increasean in copper/zinc superoxide dismutase activity (p<0.01). Reduced glutathione level in liver and plasma and concentration of sulfhydryl groups were not significantly changed by cadmium. The present study suggests that lipid peroxidation plays an important role in acute cadmium-induced liver injury. Antioxidant capacity of hepatocytes is partly increased due to an adaptive increase of superoxide dismutase activity.

Effects of Cadmium Exposure on the Ultrastructural Pathology of Different Pulmonary Cells, Leukocyte Count, and Activity of Glutathione Peroxidase and Lactate Dehydrogenase in Relation to Free Radical Production in Uromastyx aegyptius

Animal studies on the toxicity of heavy metals have been widely used as model to simulate the impacts of environmental pollution on the human health. In the present study the authors hypothesized that cadmium exposure inducts changes in reactive oxygen species (ROS) and that may be involved in the pathogenesis of lung diseases. The pathological changes of different pulmonary cells of ROS-cadmium-dependent effects were investigated in relation to the activity of lactate dehydrogenase (LDH) and glutathione peroxidase (GPx). Twelve animals were randomly assigned to two groups, control and experimental. The experimental group underwent ingestion of cadmium mixed with diet (200 mg/kg) for 7 weeks. Following the treatment conditions for each group, blood samples were collected and animals were sacrificed and the lung was isolated. Ultrastructure examination showed that cadmium resulted in desquamated pneumocyte type II with degenerated surfactant materials, thickened alveolar wall, and thickening of alveolar septum due to proliferation of endothelial cells lining the pulmonary capillaries as a result of an active transmigration. t-test results showed that cadmium caused a significant (p < .05) rise in leukocytes, lymphocytes, neutrophils, and monocytes, which was a sign for chemotactic activity that enhanced transmigration from pulmonary microcirculation into inflammated tissue. In addition, lung tissue FR production, LDH, and GPx activities increased significantly (p < .05) from the baseline control of 88.17±17.70, 183.49±29.50, and 4466.79±1190.32 to 129.67±14.49.14 (Carr U), 339.17±75.28 (U/L), and 5943.08±695 (U/L) respectively, in the cadmium-treated group. Based on the results of the present study, it can be concluded that long-term cadmium exposure (ingestion mixed with food) results in cadmium deposition in the tissue of the vasculature of the lungs, such as pulmonary capillary endothelial, which induced the buildup of ROS, a possible proposed new mechanism that explains lung inflammation.

Protective role of selenium against renal toxicity induced by cadmium in rats

Cadmium is an environmental toxic metal implicated in human diseases. The mechanism of its toxicity is not fully understood. Therefore, the role of cadmium in renal toxicity, and the protective role of selenium against this toxicity were investigated. Forty-five male rats were used through out the study and divided into three groups of 15. The first group received saline solution daily for 10 days. The second group, received cadmium chloride (CdCl 2) (2 mg/kg body weight) intraperitoneally daily for a period of 10 days. The third group, received sodium selenite (1 mg/kg body weight, twice a day) and CdCl 2 (once a day) for a period of 10 days. The results showed that cadmium treatment increased renal lipid peroxidation (measured as malondialdehyde, MDA) which was associated with a significant decrease in the antioxidant systems such as reduced glutathione levels and the activities of glutathione peroxidase (GPx) and thioredoxin reductase (TrxR). On the other hand, pretreatment of rats with selenium and cadmium led to a significant decrease in MDA concentration, and increased levels of GSH and the activities of GPx and TrxR when compared with those of cadmium-treated group. The total levels of phospholipid, triglyceride, and cholesterolester classes were decreased, while free fatty acids levels were markedly increased after cadmium treatment. In addition, the total levels of both mono- and poly-unsaturated fatty acids of different lipid classes were significantly decreased, while the total saturated fatty acids was significantly increased by cadmium treatment. Pretreatment of rats with selenium, was found to protect kidney tissues of rats against the biochemical changes resulting from cadmium administration. These results suggest that cadmium causes renal toxicity by inducing lipid peroxidation, decreasing antioxidant systems, and also by altering lipid metabolism. In addition, selenium treatment could protect the kidney tissues against the toxicity of cadmium since it reduced MDA levels and increased the activities of antioxidant enzymes in these tissues. These results could be important for the further understanding of the complex mechanisms of cadmium toxicity in kidney tissues and in the development of better treatments for people and/or animals exposed to the heavy metal.

Fertility and content of cadmium in pheasant (Phasianus colchicus) following cadmium intake in drinking water

In this study, the effects of cadmium applied per os on fertility, live weight of newly hatched chicks, and cadmium concentrations in some organs of young and adult pheasants were investigated. The metal was applied at the concentration of 1.5 mg Cd 2+/L during 3 months. After the egg laying, the numbers of eggs laid, cracked, and unfertilized were determined and the live weights of newly hatched chicks were measured. The cadmium concentrations in liver, kidney, and muscle ( m. pectoralis) of young and adult pheasants were analyzed. We found that cadmium exposure of the adults did not affect the number of eggs laid but resulted in more eggs being damaged. Hatchlings were significantly heavier in the cadmium-treated group (21.36±2.28 g) compared to the control group (20.91±1.97 g) 4 weeks after the cadmium intake. Higher cadmium concentrations were observed in the muscle and kidney tissue of newly hatched pheasants after 4 weeks compared to the cadmium-exposed groups after 8 and 12 weeks. The cadmium concentrations in kidneys and liver increased significantly in adult pheasants. The metal had accumulated especially in kidneys of the adult pheasants and reached levels up to 9.64 mg/kg wet weight 3 months after the daily cadmium intake in drinking water. The concentration in liver of the adults was 3.53 mg/kg wet weight.

Effect of Dietary Cadmium Levels on Nutrient Digestibility and Retention of Iron, Copper and Zinc in Tissues of Growing Pigs

This experiment was conducted to investigate the effect of cadmium levels on weight gain, nutrient digestibility and the retention of iron, copper and zinc in tissues of growing pigs. A total of one hundred and ninety-two crossbred pigs (barrows, Duroc×Landrace×Yorkshine, 27.67±1.33 kg of average initial body weight) were randomly allotted to four treatments. Each treatment had three replicates with 16 pigs per pen. The corn-soybean basal diets were supplemented with 0, 0.5, 5.0, 10.0 mg/kg cadmium respectively, and the feeding experiment lasted for eight-three days. Cadmium chloride was used as cadmium source. The results showed that pigs fed the diet containing 10.0 mg/kg cadmium had lower ADG and FCR than any other treatments (p<0.05). Apparent digestibility of protein in 10.0 mg/kg cadmium-treated group was lower than that of other groups (p<0.05). There was lower iron retention in some tissues of 5.0 mg/kg and 10.0 mg/kg cadmium treatments (p<0.05). However, pigs fed the diet 10.0 mg/kg cadmium had higher copper content in most tissues than that of any other groups (p<0.05). There was a significantly increase of zinc retention in kidney of 10.0 mg/kg cadmium additional group (p<0.05) and zinc concentrations in lymphaden, pancreas and heart of 10.0 mg/kg cadmium treatment were lower than those of the control (p<0.05). This study indicated that relatively high cadmium level (10.0 mg/kg) could decrease pig growth performance and change the retention of iron, copper and zinc in most tissues during extended cadmium exposure period. (Asian-Aust. J. Anim. Sci. 2004. Vol 17, No. 7 : 1007-1013)

Cadmium-induced ectopic apoptosis in zebrafish embryos.

In this study, we tested the hypothesis that cadmium-induced developmental toxicity was mediated via ectopic occurrence of apoptosis during embryonic development. We employed confocal microscopy to acquire images of whole-mount staining of apoptotic cells in zebrafish embryo exposed to 100 micro M cadmium from 5 hours post fertilisation (hpf) to 28 hpf. Three-dimensional reconstruction of the images was performed and the spatial and temporal distributions of apoptotic cells in the embryos were compared. In cadmium-treated embryos with varying degrees of gross developmental malformations, significantly higher numbers of apoptotic cells were detected with this method. In order to detect the precise locations of apoptotic cells, we performed terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay in sectioned embryos. In the degenerating neural tube of cadmium-treated embryos apoptotic cells were detected, while in the healthy neural tube of the untreated controls no apoptotic cells were found. We then employed flow cytometry to investigate whether cadmium exposure would affect the dynamics of apoptosis or induce any abnormalities in cell-cycle progression. It appeared that cadmium did not induce cell-cycle arrest. The percentages of apoptotic cells did not differ in the two groups at 13, 16 or 19 hpf. At 28 hpf, however, a significantly higher percentage of apoptotic cells were found in the cadmium-treated group. Exposure to cadmium, therefore, induced ectopic apoptosis at 28 hpf without affecting the dynamics of apoptosis at earlier developmental stages.

Acute effects of cadmium on the renin angiotensin system in rats

The effect of cadmium acetate (1 μg/kg i.p.) on the renin angiotensin system was examined in male Sprague-Dawley rats. Blood pressure, plasma renin activity (PRA) and serum angiotensin converting enzyme (ACE) levels were determined in the rats. Cadmium acetate produced a hypertensive response which was not associated with elevated PRA. However, ACE levels in the serum were significantly decreased in the cadmium-treated group as compared with normal controls (P < 0.01).

Chronic carcinogenic and toxic effects of a single subcutaneous dose of cadmium in the male fischer rat

The carcinogenic effects of cadmium have not been thoroughly assessed in the commonly used Fischer (F344) rat. This study determined tumor incidence in various tissues of male F344/NCr rats after a single dose of cadmium. Cadmium (as CdCl2) was given sc in the dorsal thoracic midline at 30 mumole/kg to 70 8-week old male F344 rats while controls (n = 50) received saline. Rats were observed during the next 90 weeks. Early deaths (less than or equal to 32 weeks), due mostly to acute cadmium-induced hepatotoxicity, accounted for 37 of the cadmium-treated rats while no control rats died in the same period. A high incidence of injection site sarcomas (ISS) occurred in the cadmium-treated group (21 ISS/32 rats at risk; 66%) while only 1/50 occurred in controls (2%). In fact, ISS were the major cause of morbidity after 35 weeks in cadmium-treated rats. These tumors were mostly fibrosarcomas, although histiocytic and osteogenic sarcomas also occurred. Testicular interstitial cell tumors, which show a very high spontaneous incidence in this strain (41/49; 84%), were not markedly affected by cadmium (30/31; 97%). This is in sharp contrast to other strains, such as the Wistar, in which cadmium treatment is reported to cause as much as an eightfold increase in interstitial cell (Leydig cell) tumor incidence. The incidence of large granular lymphocyte (LGL) leukemia, which also occurred frequently in control F344 rats (12/47; 26%) was markedly decreased (2/31; 7%) by cadmium. Our recent studies indicate acute lymphonecrotic effects occur with cadmium in lymphoid tissues of rats, and this may be related to the suppression of the leukemia. These results indicate that cadmium is very effective in inducing ISS in F344 rats, as is the case with other strains thus far tested, and also markedly reduces spontaneous leukemia incidence.

Effect of intratracheal instillation of cadmium chloride on phospholipids in alveolar wash fluid

The effect of cadmium chloride on phospholipids in the alveolar wash fluid was investigated by instilling the chemical (2.5 μg Cd/0.4 ml saline per rat) into rat trachea. Two days later the phospholipid content of the was fluid increased markedly in the cadmium-treated group to about 2.4 times that in the control (saline-treated) group. The relative amount of phosphatidylcholine and the fatty acid composition of phosphatidylcholine were not altered by the cadmium treatment, and retained a composition typical of lung surfactant. These findings suggest that cadmium induces a marked increase in surfactant phospholipids in the lung at a very low dose.

Calcium Accumulation in Rat Liver after Oral Administration of Lead or Cadmium

The amount of calcium in the liver of rats was examined after continuous oral administration of 0.1 mg/day of lead or cadmium acetate for 30 days, and the following results were obtained. The amount of calcium in the liver increased about 3 times (p<0.01) in the lead-treated group, but decreased to about one-half (p<0.01) in the cadmium-treated group compared with control group. On the other hand, the liver calcium concentration in both lead and cadmium-treated group increased significantly compared with that of the cadmium-treated group. These data suggest that lead antagonizes the effect of cadmium on the amount of calcium in the liver of rats.