Effect of Co-EDTA on hematological parameters in immature mice (original) (raw)
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Effect of Cobalt-Edta on Iron Content in Spleen and Liver of Immature Mice
European Chemical Bulletin, 2012
Cobalt (Co) is an essential trace element and its accumulation affects the concentrations of other elements. Co(II) is shown to compete with iron (Fe) for the transferrin receptor and to form a stable complex with hemoglobin thus affecting hematopoiesis. There are lack of data regarding the effect of chronic exposure to Co compounds and Fe content in spleen and liver of mice. The study investigates the effect of long-term treatment with cobalt-EDTA (Co-EDTA) on iron content in the spleen and liver of immature mice. Pregnant ICR mice were subjected to chronic treatment with daily dose of 75 mg/kg Co-EDTA which continued until d25 of the newborn pups. Results show accumulation of Co(II) in the organs of treated mice compared to age-matched controls. Fe content in the spleen and liver was affected as well. Significantly increased concentrations of Fe ions were measured in the livers of treated mice. The changes could explain impaired hematopoiesis and immune responses of exposed to Co(...
Biotechnology & Biotechnological Equipment, 2012
Cobalt (Co) and its compounds are shown to improve hematological parameters. Long-term treatment with Co(II) increased hemoglobin content in a dose-and time-dependent manner in mature mice (day 45 to day 90) while it was reduced in immature mice (day 18 to day 30). Higher Hb was measured in samples treated with CoCl 2 compared to those treated with Co-EDTA. Plasma Fe concentration was significantly higher in samples treated with Co-EDTA compared to those exposed to CoCl 2. Lower concentrations were measured only in mature animals. Co(II) concentration increased but not in a dose-dependent manner. In general more Co(II) was measured in samples treated with CoCl 2 possibly due to the stability of the complex Co-EDTA. Surprisingly, mature mice had less Co(II) in their plasma compared to day 18 mice. Strong correlation between plasma Co(II) and iron concentration was found in samples of mice treated with Co-EDTA. Co(II) concentration showed inverse correlation with hemoglobin in mice treated with low dose Co-EDTA. Such relationship was found for day 45 and day 60 mice exposed to high dose CoCl 2. Immature mice are more sensitive to Co(II) treatment and show signs of anemia. It has a significant impact on hemoglobin biosynthesis possibly due to its effect on iron metabolism.
Cobalt Bioaccumulation in Mouse Blood Plasma and Liver
Biotechnology & Biotechnological Equipment, 2010
Heavy metals such as cobalt are shown to accumulate in various organs of humans and animals. Oral exposure of immature mice to cobalt compounds (cobalt chloride and cobalt-EDTA) led to significant increase in cobalt (II) concentration in blood plasma and liver. Pregnant balb/c mice in late gestation were subjected to cobalt chloride (CoCl 2 .6H 2 O) or cobalt EDTA (Co-EDTA) treatment at daily doses of 75 mg/kg or 125 mg/kg which continued until day 30 of the newborn mice. Cobalt salts were dissolved and obtained from drinking tap water. Pure tap water was used as control. Mice were maintained in individual standard hard bottom polypropylene cages to ensure that all experimental animals obtained the required dose of cobalt salts. The newborn pups were sacrificed on days 18, 25 and 30 which correspond to different stages of development. Mice were weighed weekly and the experimental cobalt concentration was adjusted accordingly. Blood plasma and liver were used for measuring cobalt bioaccumulation. Cobalt (II) compounds showed differential bioaccumulation: higher concentrations were measured in the plasma compared to those measured in the liver. The effect depended on the type of compound used, dose, time duration as well as on the age of the experimental animals. Higher metal concentrations were detected in samples of mice treated with cobalt chloride compared to the samples exposed to Co-EDTA. The results indicate that day 18 mice are more sensitive to chronic exposure to cobalt compounds in high doses. Cobalt(II) concentrations in blood plasma may be used as a useful marker for diagnosing chronic exposure to cobalt compounds.
Cobalt Chloride Treatment and Iron Metabolism in Immature Mice
2014
Although cobalt is an essential trace element, it is toxic in high concentrations. Long-term exposure to cobalt chloride (CoCl2) significantly increases Co(II) ions in blood serum, spleen and liver of treated immature mice compared to controls and induces changes in the iron (Fe) content. Spleen and liver show different sensitivity to Co(II) administration but increase iron storage. The three experimental groups of immature mice - day 18-, 25- and 30, used in the experimental design, show different sensitivity to the metal. This suggests that the stage of development is also an important marker that should be considered.
Effect of Chronic Exposure to Cobalt ( II ) Compounds on Organs ’ Weight Indices
2016
Cobalt’s (Co) wide use in the industry, in medical devices, as food perservative, in consmetics requires detailed study on its biological effects. The aim of the study was to elucidate the effect of chronic treatment with cobalt(II) compounds – cobalt chloride (CoCl2) and cobalt-EDTA (Co-EDTA) on organ weight indices in immature and mature mice. Pregnant ICR mice were treated daily with 75 mg/kg b.w. or 125 mg/kg b.w. of CoCl2 or Co-EDTA until day 90 of the newborn mice. The compounds were dissolved in regular tap water. The control mice obtained regular tap water. All experimental animals obtained food ad libitum. On day 25 pn the newborn mice were placed in individual cages and the treatment continued until day 90. Each week mice were weighed to adjust the dose. At different periods – day 18, 25, 30, 45, 60 and 90 mice were sacrificied. Spleens, liver and kidneys were excised, weighed and organ weight indices spleen index (SI), liver index (LI) and kidney index (KI) calculated. Ch...
Effects and blood concentrations of cobalt after ingestion of 1 mg/d by human volunteers for 90 d
American Journal of Clinical Nutrition, 2014
Over-the-counter cobalt supplements are available for sale in the United States, but little is known regarding their clinical effects and biokinetic distribution with long-term use. We assessed blood kinetics, biochemical responses, and clinical effects in 5 adult men and 5 adult women who voluntarily ingested ∼ 1.0 mg Co/d (0.080-0.19 mg Co · kg⁻¹ · d⁻¹) of a commercially available cobalt supplement over a 3-mo period. Volunteers were instructed to take the cobalt dietary supplement in the morning according to the manufacturer's label. Blood samples were collected and analyzed for a number of biochemical variables before, during, and after dosing. Hearing, vision, cardiac, and neurologic functions were also assessed in volunteers before, during, and after dosing. After ∼ 90 d of dosing, mean cobalt blood concentrations were lower in men than in women. Mean cobalt whole blood and serum concentrations in men were 20 μg/L (range: 12-33 μg/L) and 25 μg/L (range: 15-46 μg/L), respectively. In women, mean cobalt whole blood and serum concentrations were 53 μg/L (range: 6-117 μg/L) and 71 μg/L (range: 9-149 μg/L), respectively. Estimated red blood cell (RBC) cobalt concentrations suggested that cobalt was sequestered in RBCs during their 120-d life span, which resulted in a slower whole blood clearance compared with serum. The renal clearance of cobalt increased with the serum concentration and was, on average, lower in women (3.5 ± 1.3 mL/min) than in men (5.5 ± 1.9 mL/min). Sex-specific differences were observed in cobalt absorption and excretion. There were no clinically significant changes in biochemical, hematologic, and clinical variables assessed in this study. Peak cobalt whole blood concentrations ranging between 9.4 and 117 μg/L were not associated with clinically significant changes in basic hematologic and clinical variables.
Acute exposure to cobalt induces transient methemoglobinuria in rats
Toxicology Letters, 2004
We observed transient excretion of dark-brown urine after acute exposure to cobalt in rats and investigated the mechanism of it. We injected cobalt into rats s.c. at a dose of 15 mg/kg and collected urine, peripheral blood, and organ samples at the indicated times after injection. Biochemical and histopathological examinations of these samples were conducted. Obvious macroscopic and biochemical methemoglobinuria was observed just after injection of cobalt, but the level of urinary methemoglobin decreased gradually, almost disappearing by 24 h. The levels of cobalt in peripheral blood and urine showed a very similar pattern to that of methemoglobinuria. Neither anemia nor bilirubinemia was observed, indicating no extrarenal intravascular hemolysis. Pathological examination of the kidneys revealed that the glomerular capillaries were filled with red blood cells at 1 h after injection. Electron microscopy showed deformed red blood cells in the glomerular capillaries and condensed hemoglobin in Bowman's capsule that passed through the basement membrane. There were no trends toward increases in plasma levels of creatinine or blood urea nitrogen. These results indicate that exposure to cobalt induces transient methemoglobinuria through the lysis of red blood cells and oxidation of iron in hemoglobin at the glomerular capillaries without causing renal dysfunction.
Cobalt chloride induces hepatotoxicity in adult rats and their suckling pups
Experimental and Toxicologic Pathology, 2011
To assess liver damages in pregnant and lactating rats and in their suckling pups, wistar female rats were given through drinking water 350 ppm of CoCl 2 (157 ppm Co 2 + ) from the 14th day of pregnancy until day 14 after delivery. The effects of cobalt chloride on lipid peroxidation levels, antioxidant enzyme activities, lipid profile and histopathology aspects of liver were evaluated. Biochemical results showed that lipid peroxidation increased significantly in Co-treated rats, as evidenced by high liver thiobarbituric acid-reactive substance (TBARS) levels. Alteration of the antioxidant system in treated group was confirmed by the significant decline of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content in liver of suckling pups and their mothers. Moreover, CoCl 2 exposure induced an increase in the activities of the aspartate transaminase (AST), alanine transaminase (ALT), lactate deshydrogenase (LDH) and bilirubin levels in pups and their mothers while liver LDH activity and plasma albumin level were significantly decreased. On the other hand, cobalt chloride induced a marked hypoglycemia, a significant decline in triglycerides and total cholesterol levels. Histological studies showed an infiltration of mononuclear cells and vascular congestion in liver of pups and their mothers.
Erythropoietic effects of low-dose cobalt application
Drug Testing and Analysis
Cobaltous ions (Co 2+) stabilize HIFα, increase endogenous erythropoietin (EPO) production, and may, therefore, be used as a performance-enhancing substance. To date, the dosage necessary to stimulate erythropoiesis is unknown. The aim of this study was, therefore, to determine the minimum dosage necessary to increase erythropoietic processes. In a first double-blind placebo-controlled study (n = 5), single oral Co 2+ dosages of 5 mg (n = 6) and 10 mg (n = 7) were administered to healthy young men. Cubital venous blood and urine samples were collected before and up to 24 hours after Co 2+ administration. In a second study, the same daily Co 2+ dosages were administered for five days (placebo: n = 5, 5 mg: n = 9, 10 mg: n = 7). Blood and urine samples were taken the day before administration and at day 3 and day 5. Plasma [EPO] was elevated by 20.5 ± 16.9% at 5 hours after the single 5-mg administration (p < 0.05) and by 52.8 ± 23.5% up to 7 hours following the 10-mg Co 2+ administration (p < 0.001). Urine [Co 2+ ] transiently increased, with maximum values 3-5 hours after Co 2+ ingestion (5 mg: from 0.8 ± 1.1 to 153.6 ± 109.4 ng/mL, 10 mg: from 1.3 ± 1.7 to 338.0 ± 231,5 ng/mL). During the five days of Co 2+ application, 5 mg showed a strong tendency to increase [EPO], while the 10-mg application significantly increased [EPO] at day 5 by 27.2 ± 26.4% (p < 0.05) and the immature reticulocyte fraction by 49.9 ± 21.7% (p < 0.01). [Ferritin] was decreased by 12.4 ± 10.4 ng/mL (p < 0.05). An oral Co 2+ dosage of 10 mg/day exerts clear erythropoietic effects, and 5 mg/day tended to increase plasma EPO concentration.
Urinary cobalt and ferritin in four-years-old children
Environmental Research, 2020
Cobalt (Co) is an essential trace element but may cause toxic effects upon occupational or 25 environmental exposure. The present study is aimed to determine the urine concentrations of Co in 26 four years-old children in the INMA-Asturias cohort (Spain) and to assess the factors determining 27 the observed levels. This cohort is located in a heavily industrialized zone with strong potential for 28 metal exposure. 29 Some diet components such as consumption of sweets were meaningfully associated with 30 higher urine Co concentrations. Traffic pollution also showed a noteworthy positive association 31 with Co levels. Family tobacco consumption did not show substantial association with the urine 32 concentrations of this metal in the INMA-Asturias children. 33 A significant inverse association between urine Co and venous blood ferritin was found. 34 Iron deficiency anemic children had significantly higher concentrations of Co than those with 35 normal levels, e.g. median values 1.9 µg/g creatinine and 1.0 µg/g creatinine, respectively. This 36 association could be explained by an increased expression of DMT1, a divalent metal transporter 37 that captures higher levels of iron in deficiency states of this metal. This transporter is non-specific 38 and not only captures iron but also other divalent metals such as Co. The presence of this metal in iron deficiency anemic children may represent an additional disturbing health factor that must be 40 considered during treatment. 42 Human metabolism uses this trace metal for cobalamin synthesis (vitamin B12) whose 49 deficiency causes a wide range of hematological, gastrointestinal, psychiatric and neurological 50 disorders (Briani et al., 2013). However, only a small fraction of Co intake is used for this purpose 51 and the remaining ingested amounts are inorganic compounds with no essential function (Kim et 52 al., 2006). 53 Gastrointestinal absorption of dietary Co can typically range from 10 to 35% (Unice et al., 54 2012). Intakes of 20% and 45% in males and females, respectively, are considered standard 55 reference values in human biokinetic models (Unice et al., 2014). Cobalt deficiency has never been 56 described in human metabolism (Simonsen et al., 2012). Occupational and accidental exposures to 57 Co have been reported to originate asthma, allergic alveolitis, hypersensitivity pneumonitis, 58