Assessing Cobalt Metal Nanoparticles Uptake by Cancer Cells Using Live Raman Spectroscopy.

PURPOSE: Nanotechnology applied to cancer treatment is a growing area of research in nanomedicine with magnetic nanoparticle-mediated anti-cancer drug delivery systems offering least possible side effects. To that end, both structural and chemical properties of commercial cobalt metal nanoparticles were studied using label-free confocal Raman spectroscopy. MATERIALS AND METHODS: Crystal structure and morphology of cobalt nanoparticles were studied by XRD and TEM. Magnetic properties were studied with SQUID and PPMS. Confocal Raman microscopy has high spatial resolution and compositional sensitivity. It, therefore, serves as a label-free tool to trace nanoparticles within cells and investigate the interaction between coating-free cobalt metal nanoparticles and cancer cells. The toxicity of cobalt nanoparticles against human cells was assessed by MTT assay. RESULTS: Superparamagnetic Co metal nanoparticle uptake by MCF7 and HCT116 cancer cells and DPSC mesenchymal stem cells was investigated by confocal Raman microscopy. The Raman nanoparticle signature also allowed accurate detection of the nanoparticle within the cell without labelling. A rapid uptake of the cobalt nanoparticles followed by rapid apoptosis was observed. Their low cytotoxicity, assessed by means of MTT assay against human embryonic kidney (HEK) cells, makes them promising candidates for the development of targeted therapies. Moreover, under a laser irradiation of 20mW with a wavelength of 532nm, it is possible to bring about local heating leading to combustion of the cobalt metal nanoparticles within cells, whereupon opening new routes for cancer phototherapy. CONCLUSION: Label-free confocal Raman spectroscopy enables accurately localizing the Co metal nanoparticles in cellular environments. The interaction between the surfactant-free cobalt metal nanoparticles and cancer cells was investigated. The facile endocytosis in cancer cells shows that these nanoparticles have potential in engendering their apoptosis. This preliminary study demonstrates the feasibility and relevance of cobalt nanomaterials for applications in nanomedicine such as phototherapy, hyperthermia or stem cell delivery.

Hierarchical porous Mg2SiO4-CoFe2O4 nanomagnetic scaffold for bone cancer therapy and regeneration: Surface modification and in vitro studies.

3D multifunctional bone scaffolds have recently attracted more attention in bone tissue engineering because of addressing critical issues like bone cancer and inflammation beside bone regeneration. In this study, a 3D bone scaffold is fabricated from Mg2SiO4-CoFe2O4 nanocomposite which is synthesized via a two-step synthesis strategy and then the scaffold's surface is modified with poly-3-hydroxybutyrate (P3HB)-ordered mesoporous magnesium silicate (OMMS) composite to improve its physicochemical and biological properties. The Mg2SiO4-CoFe2O4 scaffold is fabricated through polymer sponge technique and the scaffold exhibits an interconnected porous structure in the range of 100-600 µm. The scaffold is then coated with OMMS/P3HB composite via dip coating and the physical, chemical, and biological-related properties of OMMS/P3HB composite-coated scaffold are assessed and compared to the non-coated and P3HB-coated scaffolds in vitro. It is found that, on the one hand, P3HB increases the cell attachment, proliferation, and compressive strength of the scaffold, but on the other hand, it weakens the bioactivity kinetic. Addition of OMMS to the coating composition is accompanied with significant increase in bioactivity kinetic. Besides, OMMS/P3HB composite-coated scaffold exhibits higher drug loading capacity and more controlled release manner up to 240 h than the other samples because of OMMS which has a high surface area and ordered mesoporous structure suitable for controlled release applications. The overall results indicate that OMMS/P3HB coating on Mg2SiO4-CoFe2O4 scaffold leads to a great improvement in bioactivity, drug delivery potential, compressive strength, cell viability, and proliferation. Moreover, OMMS/P3HB composite-coated scaffold has heat generation capability for hyperthermia-based bone cancer therapy and so it is suggested as a multifunctional scaffold with great potentials for bone cancer therapy and regeneration.

Erythropoietic effects of low-dose cobalt application.

Cobaltous ions (Co2+ ) 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 Co2+ 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 Co2+ administration. In a second study, the same daily Co2+ 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 Co2+ administration (p < 0.001). Urine [Co2+ ] transiently increased, with maximum values 3-5 hours after Co2+ 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 Co2+ 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 Co2+ dosage of 10 mg/day exerts clear erythropoietic effects, and 5 mg/day tended to increase plasma EPO concentration.

The Effect of Maternal Supplementation of Zinc, Selenium, and Cobalt as Slow-Release Ruminal Bolus in Late Pregnancy on Some Blood Metabolites and Performance of Ewes and Their Lambs.

The aim of this study was to determine the effect of the supplementation of a slow-release bolus of zinc (Zn), selenium (Se), and cobalt (Co) at late gestation (6 week prepartum) on performance and some blood metabolites of Mehraban ewes and their lambs until weaning. Seventy pregnant ewes, 6 weeks prior to expected lambing, were randomly divided into two groups (35 heads each) including (1) control group and (2) slow-release bolus group. Blood samples of ewes were obtained on day 10 prepartum and 45 and 90 days postpartum, and milk samples were collected on day 45. Blood samples of lambs were collected on days 10, 45, and 90. Body weight at birth and weaning and average daily gain were higher and percentage of mortality and white muscle disease rate were lower in lambs whose mothers were given a bolus (P < 0.05). Slow-release bolus administration increased serum alkaline phosphatase and whole blood glutathione peroxidase activity, plasma concentrations of Zn, Se, and vitamin B12 in ewes and their lambs (P < 0.05). In addition, serum creatine phosphokinase activity of lambs whose mothers were given bolus was lower (P < 0.05). Serum concentration of T3 in bolus given ewes and their lambs was higher (P < 0.05) and serum T4 concentration was lower (P < 0.05). Zinc, Se, and vitamin B12 concentrations in milk were significantly higher in treated ewes (P < 0.05). Obtained results showed that maternal supplementation of zinc, selenium, and cobalt as slow-release ruminal bolus in late pregnancy improved some mineral status of ewes and their lambs until weaning and led to higher body weights of lambs at weaning.

Comparative study of the tissue distribution of equimolar repeated doses of hydroxocobalamin and cobalt chloride in the rats.

High dose of the cobalt atom is toxic for mammals. Hydroxocobalamin is considered safe due to the inclusion of the cobalt atom into the heminic moiety. The tissue distribution of cobalt following repeated doses of either hydroxocobalamin or cobalt chloride was studied in Wistar rats. In both cases, cobalt was administered in equimolar doses daily for an overall period of three weeks. Three groups were designed. In the hydroxocobalamin treated group, ten rats received hydroxocobalamin 17.5 mg by intraperitoneal route daily. In the cobalt-treated group, ten rats received cobalt chloride 3 mg i.p. daily. In the control group, six rats received a daily injection of 0.35 mL isotonic sodium chloride i.p. Cobalt concentrations were measured by Inductively Coupled Plasma Atomic Emission. Ours results showed that in rats having received either hydroxocobalamin or cobalt chloride, the tissue concentrations of cobalt were greater than those in the control group. The present study documented that in naive rats, the repeated administration of high doses of cobalt as hydroxocobalamin leads to tissue concentrations of the atom of cobalt significantly lower than those induced by equimolar doses of cobalt administered as cobalt chloride (p <0.05). We conclude that hydroxocobalamin reduced the tissue distribution of the cobalt atom in comparison with cobalt chloride.

Pharmacokinetics of inorganic cobalt and a vitamin B12 supplement in the Thoroughbred horse: Differentiating cobalt abuse from supplementation.

BACKGROUND: While cobalt is an essential micronutrient for vitamin B12 synthesis in the horse, at supraphysiological concentrations, it has been shown to enhance performance in human subjects and rats, and there is evidence that its administration in high doses to horses poses a welfare threat. Animal sport regulators currently control cobalt abuse via international race day thresholds, but this work was initiated to explore means of potentially adding to application of those thresholds since cobalt may be present in physiological concentrations. OBJECTIVES: To devise a scientific basis for differentiation between presence of cobalt from bona fide supplementation and cobalt doping through the use of ratios. STUDY DESIGN: Six Thoroughbred horses were given 10 mL vitamin B12 /cobalt supplement (Hemo-15® ; Vetoquinol, Buckingham, Buckinghamshire, UK., 1.5 mg B12 , 7 mg cobalt gluconate = 983 µg total Co) as an i.v. bolus then an i.v. infusion (15 min) of 100 mg cobalt chloride (45.39 mg Co) 6 weeks later. Pre-and post-administration plasma and urine samples were analysed for cobalt and vitamin B12 . METHODS: Urine and plasma samples were analysed for vitamin B12 using an immunoassay and cobalt concentrations were measured via ICP-MS. Baseline concentrations of cobalt in urine and plasma for each horse were subtracted from their cobalt concentrations post-administration for the PK analysis. Compartmental analysis was used for the determination of plasma PK parameters for cobalt using commercially available software. RESULTS: On administration of a vitamin B12 /cobalt supplement, the ratio of cobalt to vitamin B12 in plasma rapidly increased to approximately 3 and then rapidly declined below a ratio of 1 and then back to near baseline over the next week. On administration of 100 mg cobalt chloride, the ratio initially exceeded 10 in plasma and then declined with the lower 95% confidence interval remaining above a ratio of 1 for 7 days. For two horses with extended sampling, the plasma ratio remained above one for approximately 28 days after cobalt chloride administration. The effect of the administration of the vitamin B12 /cobalt supplement on the urine ratio was transient and reached a peak value of 10 which then rapidly declined. However, a urine ratio of 10 was exceeded, with the lower 95% confidence interval remaining above a ratio of 10 for 7 days after cobalt chloride administration. For the two horses with extended sampling, the urine ratio remained above 10 for about 18 days (442 h) after cobalt chloride administration even though the absolute cobalt urine concentration had dropped below the international threshold of 100 ng/mL after 96 h. MAIN LIMITATIONS: Only one vitamin B12 /cobalt product was evaluated, a limited number of horses were included, the horses were not in full race training and the results may be specific to this population of horses. CONCLUSIONS: The results provide the basis for a potential strategy for allowing supplementation with vitamin B12 products, while controlling the misuse of high doses of cobalt, through a combination of international thresholds and ratios of cobalt to vitamin B12 , in plasma and urine.

Towards the elimination of excessive cobalt supplementation in racing horses: A pharmacological review.

Cobalt is an essential trace element for many vital physiological functions. Cobalt is also known to stabilise hypoxia-inducible transcription factors leading to increased expression of erythropoietin which activates production of red blood cells. This implies that cobalt can be used to enhance aerobic performance in racing horses. If this becomes a pervasive practice, the welfare of racing animals would be at risk because cobalt is associated with cardiovascular, haematological, thyroid gland and reproductive toxicity as observed in laboratory animals and humans. It is expected that similar effects may manifest in horses but direct evidence on equine specific effects of cobalt and the corresponding exposure conditions leading to such effects is lacking. Available pharmacokinetic data demonstrates that intravenously administered cobalt has a long elimination half-life (42-156 h) and a large volume of distribution (0.94 L/kg) in a horse implying that repeated administration of cobalt would accumulate in tissues over time attaining equilibrium after ~9-33 days. Based on these pharmacokinetic data and surveys of horses post racing, threshold cobalt concentrations of 2-10 µg/L in plasma and 75-200 µg/L in urine have been recommended. However, there is no clearly defined, presumably normal cobalt supplementation regimen for horses and characterisation of potential adverse effects of any established threshold cobalt concentrations has not been done. This review outlines the strengths and limitations of the existing literature on the pharmacological effects of cobalt in horses with some recommendations on what gaps to bridge to enable the determination of optimal threshold cobalt concentrations in racing horses.

Effect of melatonin on element distribution in the liver tissue of diabetic rats subjected to forced exercise.

The objective of the present study was to investigate the effects of melatonin supplementation on elements in the liver of diabetic rats subjected to acute swimming exercise. Eighty adult male rats were equally divided into eight groups. Group 1, general control. Group 2, melatonin-supplemented control. Group 3, melatonin-supplemented diabetic control. Group 4, swimming control. Group 5, melatonin-supplemented swimming. Group 6, melatonin-supplemented diabetic swimming. Group 7, diabetic swimming. Group 8, diabetic control. Liver tissue samples were analyzed for lead, cobalt, molybdenum, chrome, sulphur, magnesium, manganese, sodium, potassium, phosphorus, copper, iron, calcium, zinc, selenium. The highest cobalt, chrome values were found in the groups 7, 8 and the groups 5, 6 respectively. Groups 3 and 7 had the highest copper values. Iron and potassium values were higher in the groups 1 and 4. Group 6 had increased magnesium value, and groups 6, 7, 8 were found to have the highest manganese levels. The highest lead values were found in the groups 5 and 6. Group 6 had the highest selenium levels. The highest zinc levels were established in 1 and 2. Groups 1, 2, 5 and 6 were found to have the highest calcium values. The results of our study indicate that melatonin supplementation in diabetes and forced exercise significantly alters the element metabolism in the liver (Tab. 3,Ref. 33).

Review of cobalt toxicokinetics following oral dosing: Implications for health risk assessments and metal-on-metal hip implant patients.

Cobalt (Co) can stimulate erythropoietin production in individuals at doses exceeding 25 mg CoCl2/day. Co has also been shown to exert effects on the thyroid gland, heart and nervous system at sufficient doses. The biological activity of Co is dictated by the concentration of free (unbound) ionic Co(2+). Blood concentrations, as well as, urinary excretion rates of Co are reliable biomarkers for systemic Co exposure. A recent series of human volunteer Co-supplement studies simultaneously measured Co blood and urine concentrations, as well as, Co speciation in serum, and a number of biochemical and clinical parameters. It was found in these studies that peak Co whole blood concentration as high as 117 µg/L were not associated with changes in hematological parameters such as increased red blood cell (RBC) count, hemoglobin (Hgb) or hematocrit (Hct) levels, nor with changes in cardiac, neurological or, thyroid function. Using a Co biokinetic model, the estimated Co systemic tissue concentrations (e.g., liver, kidney, and heart) following 90-days of Co-dietary supplementation with ∼1 mg Co/day were found to be similar to estimated tissue concentrations in implant patients after 10 years of exposure at continuous steady state Co blood concentration of ∼10 µg/L. This study is the first to present modeled Co tissue concentrations at various doses following sub-chronic and chronic exposure. The modeled steady state tissue Co concentrations in combination with the data on adverse health effects in humans should help in the characterization of potential hazards associated with increased blood Co concentrations due to exposure to dietary supplements or cobalt-chromium (Co-Cr) containing implants.

Quantifying cobalt in doping control urine samples--a pilot study.

Since first reports on the impact of metals such as manganese and cobalt on erythropoiesis were published in the late 1920s, cobaltous chloride became a viable though not widespread means for the treatment of anaemic conditions. Today, its use is de facto eliminated from clinical practice; however, its (mis)use in human as well as animal sport as an erythropoiesis-stimulating agent has been discussed frequently. In order to assess possible analytical options and to provide relevant information on the prevalence of cobalt use/misuse among athletes, urinary cobalt concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS) from four groups of subjects. The cohorts consisted of (1) a reference population with specimens of 100 non-elite athletes (not being part of the doping control system), (2) a total of 96 doping control samples from endurance sport athletes, (3) elimination study urine samples collected from six individuals having ingested cobaltous chloride (500 µg/day) through dietary supplements, and (4) samples from people supplementing vitamin B12 (cobalamin) at 500 µg/day, accounting for approximately 22 µg of cobalt. The obtained results demonstrated that urinary cobalt concentrations of the reference population as well as the group of elite athletes were within normal ranges (0.1-2.2 ng/mL). A modest but significant difference between these two groups was observed (Wilcoxon rank sum test, p < 0.01) with the athletes' samples presenting slightly higher urinary cobalt levels. The elimination study urine specimens yielded cobalt concentrations between 40 and 318 ng/mL during the first 6 h post-administration, and levels remained elevated (>22 ng/mL) up to 33 h. Oral supplementation of 500 µg of cobalamin did not result in urinary cobalt concentrations > 2 ng/mL. Based on these pilot study data it is concluded that measuring the urinary concentration of cobalt can provide information indicating the use of cobaltous chloride by athletes. Additional studies are however required to elucidate further factors potentially influencing urinary cobalt levels.

Refined biokinetic model for humans exposed to cobalt dietary supplements and other sources of systemic cobalt exposure.

An updated biokinetic model for human exposures to cobalt (Co) was developed based on a comprehensive set of human pharmacokinetics data collected from five male and five female volunteers who ingested ∼1 mg Co/day of a Co supplement for 3 months. Three key experimental observations from the human dosing studies were incorporated into the model: (1) an increase in the measured fraction of large molecular serum protein bound Co from 95% during dosing to 99% after dosing; (2) a linear decrease in Co red blood cell concentration after dosing; and (3) Co renal clearance consistent with estimated glomerular filtration rates and free Co²âº concentration. The model was refined by adding compartments accounting for (1) albumin bound Co in intravascular fluid (serum); (2) albumin bound Co in extravascular fluid with physiologic exchange rates of albumin bound Co between extravascular and intravascular fluid; and (3) a novel sequential cascade of compartments representing red blood cell ages between 1 and 120 days. Reasonable agreement between the modeled and measured urine, serum, and whole blood concentrations were observed (r>0.84, slope=0.79-1.0) with gastrointestinal absorption rates between 9% and 66%. In addition, model predictions agreed well with data from several external studies representing healthy human volunteers, dialysis patients, anephric patients, a Co-poisoning incident and whole body retention studies. Our revised model considerably improves the state of knowledge on human Co kinetics, and should be helpful for evaluating elevated blood Co concentrations in currently exposed populations, such as metal-on-metal (MoM) hip implant patients.

Comparison of the magnetic, radiolabeling, hyperthermic and biodistribution properties of hybrid nanoparticles bearing CoFe2O4 and Fe3O4 metal cores.

Metal oxide nanoparticles, hybridized with various polymeric chemicals, represent a novel and breakthrough application in drug delivery, hyperthermia treatment and imaging techniques. Radiolabeling of these nanoformulations can result in new and attractive dual-imaging agents as well as provide accurate in vivo information on their biodistribution profile. In this paper a comparison study has been made between two of the most promising hybrid core-shell nanosystems, bearing either magnetite (Fe3O4) or cobalt ferrite (CoFe2O4) cores, regarding their magnetic, radiolabeling, hyperthermic and biodistribution properties. While hyperthermic properties were found to be affected by the metal-core type, the radiolabeling ability and the in vivo fate of the nanoformulations seem to depend critically on the size and the shell composition.

31-day study of cobalt(II) chloride ingestion in humans: pharmacokinetics and clinical effects.

The United Kingdom Expert Group on Vitamins and Minerals concluded that ingesting cobalt (Co)-containing supplements up to 1400 µg Co/d is unlikely to produce adverse health effects. However, the associated blood Co concentrations and safety of Co-containing dietary supplements have not been fully characterized. Thus, blood Co kinetics and a toxicological assessment of hematological and biochemical parameters were evaluated following Co dietary supplementation in 5 male and 5 female volunteers who ingested approximately 1000 µg Co/d (10-19 µg Co/kg-d) as cobalt(II) chloride for a period of 31 d. Supplement intake was not associated with significant overt adverse events, alterations in clinical chemistries including blood counts and indicators of thyroid, cardiac, liver, or kidney functions, or metal sensitization. A non-clinically significant (<5%) increase in hemoglobin, hematocrit, and red blood cell (RBC) counts were observed in males but not females 1 wk after dose termination. Mean Co concentrations in whole blood/serum after 31 d of dosing were approximately two-fold higher in females (33/53 µg/L) than in males (16/21 µg/L). In general, steady-state concentrations of Co were achieved in whole blood and/or red blood cells (RBC) within 14-24 d. Temporal patterns of whole blood and serum Co concentrations indicated metal sequestration in RBC accompanied by slower whole blood clearance compared to serum. Data also indicated that peak whole blood Co concentrations up to 91.4 µg/L were not associated with clinically significant changes in clinical chemistries. In addition, Co blood concentrations and systemic uptake via ingestion were generally higher in females.

A review of the health hazards posed by cobalt.

Cobalt (Co) is an essential element with ubiquitous dietary exposure and possible incremental exposure due to dietary supplements, occupation and medical devices. Adverse health effects, such as cardiomyopathy and vision or hearing impairment, were reported at peak blood Co concentrations typically over 700 µg/L (8-40 weeks), while reversible hypothyroidism and polycythemia were reported in humans at ~300 µg/L and higher (≥2 weeks). Lung cancer risks associated with certain inhalation exposures have not been observed following Co ingestion and Co alloy implants. The mode of action for systemic toxicity relates directly to free Co(II) ion interactions with various receptors, ion channels and biomolecules resulting in generally reversible effects. Certain dose-response anomalies for Co toxicity likely relate to rare disease states known to reduce systemic Co(II)-ion binding to blood proteins. Based on the available information, most people with clearly elevated serum Co, like supplement users and hip implant patients, have >90% of Co as albumin-bound, with considerable excess binding capacity to sequester Co(II) ions. This paper reviews the scientific literature regarding the chemistry, pharmacokinetics and systemic toxicology of Co, and the likely role of free Co(II) ions to explain dose-response relationships. Based on currently available data, it might be useful to monitor implant patients for signs of hypothyroidism and polycythemia starting at blood or serum Co concentrations above 100 µg/L. This concentration is derived by applying an uncertainty factor of 3 to the 300 µg/L point of departure and this should adequately account for the fact that persons in the various studies were exposed for less than one year. A higher uncertainty factor could be warranted but Co has a relatively fast elimination, and many of the populations studied were of children and those with kidney problems. Closer follow-up of patients who also exhibit chronic disease states leading to clinically important hypoalbuminemia and/or severe ischemia modified albumin (IMA) elevations should be considered.

Cobalt-induced changes in the spleen of mice from different stages of development.

Cobalt(II) accumulates in organs such as spleen, kidneys, heart, and liver. The aim of the present study was to investigate the effects of cobalt ethylenediamine tetraacetic acid (Co-EDTA) on spleen of developing mice. Pregnant BALB/c mice in late gestation were subjected to Co-EDTA treatment at daily doses of 75 or 125 mg/kg in drinking water, which continued until d 90 of the newborn pups. The newborn pups were sacrificed on d 18, 25, 30, 45, 60, and 90, which correspond to different stages of development. Spleens were excised, weighed, and processed for histological analysis. Spleen index (SI) was calculated as a ratio of spleen weight to body weight. Cobalt(II) bioaccumulation in spleen was determined using flame atomic absorption spectrometry (FAAS). Preliminary results showed that chronic treatment of mice with low- or high-dose Co-EDTA disturbed extramedullary hematopoiesis in the spleen. The number of megakaryocytes was reduced compared to controls. SI was also reduced in d 18 mice treated with low- or high-dose Co-EDTA. However, exposure to 75 mg/kg led to an increase of SI in all other experimental groups. FAAS analysis revealed significant cobalt(II) accumulation in spleen of treated mice. The Co(II) levels in spleens of d 18 mice were highest compared to other experimental groups, indicating that at this period mice are more sensitive to treatment. Exposure to cobalt-EDTA resulted in accumulation of Co(II) in spleen, altered SI, and hematopoiesis. Immature mice appear to be more sensitive to chronic treatment than adults.

Inorganic cobalt supplementation: prediction of cobalt levels in whole blood and urine using a biokinetic model.

Soluble cobalt (Co) supplements with recommended daily doses up to 1000 µg Co/day are increasingly being marketed to consumers interested in healthy living practices. For example, some athletes may consider using Co supplements as blood doping agents, as Co is known to stimulate erythropoesis. However, the distribution and excretion kinetics of ingested Co are understood in a limited fashion. We used a Co-specific biokinetic model to estimate whole blood and urine Co levels resulting from oral exposure or ingestion of Co in amounts exceeding typical dietary intake rates. Following 10 days of Co supplementation at a rate of 400 to 1000 µg/day, predicted adult Co concentrations range from 1.7 to 10 µg/L in whole blood, and from 20 to 120 µg/L in urine. Chronic supplementation (≥ 1 year) at a rate of 1000 µg Co/day is predicted to result in blood levels of 5.7 to 13 µg/L, and in urine levels from 65 to 150 µg/L. The model predictions are within those measured in humans following ingestion of known doses. The methodology presented in this paper can be used to predict urinary or blood Co levels following acute or chronic occupational incidental ingestion, medicinal therapy, supplemental intake, or other non-occupational exposures.

Propolis attenuates cobalt induced-nephrotoxicity in adult rats and their progeny.

The aim of this study was to evaluate the biochemical changes in cobalt-exposed rats and to investigate the potential role of Tunisian propolis against the cobalt-induced renal damages. Twenty-four pregnant Wistar rats were divided into four groups and were treated as follows: group 1 (control) received distilled water; group 2 received 350 ppm of CoCl(2) in drinking water; group 3 received 350 ppm CoCl(2) in drinking water and a propolis-supplemented diet (1 g/100 g of diet); group 4 received a propolis-supplemented diet (1 g/100 g of diet) without cobalt. In the cobalt group, a significant decrease in body, absolute and relative weights was noted when compared to controls. The administration of cobalt to pregnant rats from the 14th day of pregnancy until day 14 after delivery resulted in an increased level of renal malondialdehyde, a decreased renal content of glutathione and antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase in lactating rats and their pups. A statistically significant increase in plasma urea and creatinine serum levels was seen in treated female rats and their pups. Histopathologically, the cobalt-administration induced degenerative changes in the kidney of lactating rats and their pups. When compared with cobalt-treated rats, those receiving the propolis supplementation (along with cobalt-treatment) had lower malondialdehyde levels, higher antioxidant activities and the cobalt-related histopathological changes in the kidneys were at lower severity. Our results suggested that the propolis might be a potential candidate agent against cobalt-induced nephrotoxicity in adult and juvenile rats when administered to female rats during the late pregnancy and the early postnatal period.

Novel transition metal complexes of 4-hydroxy-coumarin-3-thiocarbohydrazone: pharmacodynamic of Co(III) on rats and antimicrobial activity.

A new series of stable transition metal complexes of the formula M(L)X·S, where M = Cu(II), Ni(II), Co(III), Cr(III) and Fe(III) and L is the deprotonated ligand of 4-hydroxy-coumarin-3-thiocarbohydrazone, X = Cl(-), NO(3)(-) or CH(3)COO(-) and S = H(2)O and/or EtOH. The HL ligand was prepared by the reaction of 3-formyl-4-hydroxy-coumarine with thiocarbohydrazide in the molar ratio 1:1. The HL ligand and its metal complexes were characterized by elemental analysis, (1)H NMR, IR and electronic spectra, and molar conductance and magnetic measurements and thermal gravimetric analysis (TGA). The HL ligand acts as a monobasic tridentate ONS donor in all metal complexes, and coordinated through the phenolic OH, azomethine nitrogen and thione sulfur. Electronic spectra with magnetic moments suggested varieties of geometries around the central metal atoms. Thermal gravimetric analysis indicates that the complexes are stable up to 300°C, and release the uncoordinated and/or coordinated H(2)O/solvent molecules, which is accompanied by a color change. The formed complexes after releasing the solvent were investigated and their structures are suggested to have square planar or octahedral arrangement. Pharmacodynamic of cobalt(III) complex on some biochemical parameters and histological studies in serum and heart tissue in rats have been studied. Although the complexes demonstrated a significant effect at low dose than the high dose, the ligand showed significant good effects in both high and low doses on the biochemical analysis in serum and heart tissue. Cobalt complex was screened in order to evaluate its antifungal activity against the filamentous fungi Aspergillus niger, Aspergillus fumigatus, and Aspergillus flavus, and antibacterial activity against the Candida albicans, Escherichia coli, Klebseilla pneumoniae and Pseudomonas aeruginosa.

Trace metal concentration in Great Tit (Parus major) and Greenfinch (Carduelis sinica) at the Western Mountains of Beijing, China.

We examined the concentrations of 11 trace metals in tissues from 10 body parts of Great Tits and Greenfinches collected at Badachu Park in the Western Mountains of Beijing, China to assess the metal accumulation level, distribution among body parts, and species and gender related variations. The highest concentrations of Hg, Ni, Zn, and Mn were found in the feather; Pb and Co in the bone; Cd, Cr, and Se in the kidney, and Cu in the liver and heart. Metal concentrations had substantial interspecific variation with Great Tits showing higher levels of Hg, Cr, Ni, and Mn than Greenfinches in tissues of most body parts. Gender related variations were body part and species specific. Meta-analyses using data from this study and other studies suggested that metal concentrations of Great Tits at our study site were relatively low and below the toxic levels.

Influence of dietary cobalt source and concentration on performance, vitamin B12 status, and ruminal and plasma metabolites in growing and finishing steers.

Sixty Angus steers, averaging 274 kg, were used to evaluate the effects of Co source and concentration on performance, vitamin B12 status, and metabolic characteristics of steers. Treatments consisted of 0 (control, analyzed 0.04 mg Co/kg), 0.05, 0.10, and 1.0 mg of supplemental Co/kg of DM from CoCO3 or 0.05 and 0.10 mg of supplemental Co/kg of DM from Co propionate. Steers were individually fed a growing diet for 56 d followed by a high-concentrate finishing diet. Performance was not affected by Co supplementation during the growing phase. During the finishing phase, ADFI (DM basis) and ADG were higher (P < 0.05) for the entire finishing phase, and gain:feed was higher (P < 0.10) over the first 56 d for Co-supplemented steers. Steers supplemented with 0.10 mg Co/kg as Co propionate had higher (P < 0.05) ruminal propionate and lower (P < 0.05) acetate molar proportions than steers receiving 0.10 Co/kg as CoCO3 during the growing phase. Supplemental Co increased (P < 0.10) molar proportion of propionate during the finishing phase. Plasma vitamin B12 was higher (P < 0.05) in Co-supplemented steers by d 56 of the growing phase and remained higher (P < 0.10) throughout the study. Control steers had higher (P < 0.05) plasma methylmalonic acid on d 56 of the growing phase and on d 28, 56, and 112 of the finishing phase than steers receiving supplemental Co. Steers supplemented with Co had higher plasma glucose at d 56 (P < 0.01), 84 (P < 0.10), and 112 (P < 0.01) of the finishing phase. Steers supplemented with 0.10 mg Co/kg as Co propionate had higher plasma glucose than those receiving 0.10 mg Co/kg as CoCO3 at d 28 of the growing phase (P < 0.05) and d 28 of the finishing phase (P < 0.10). Final body weight and hot carcass weight were lower (P < 0.10) in steers receiving the control diet, whereas other carcass characteristics were not affected by dietary Co. Average daily gain and feed efficiency for the entire finishing phase did not differ among Co-supplemented steers. However, increasing supplemental Co above 0.05 mg/kg DM (total diet Co = 0.09 mg/kg) resulted in increased (P < 0.01) plasma (linear) and liver (quadratic) vitamin B12 concentrations and decreased (quadratic, P < 0.10) plasma methylmalonic acid concentrations toward the end of the finishing phase. These results suggest that finishing steers require approximately 0.15 mg Co/kg of DM. Vitamin B12 status was not affected by Co source; however, the two Co sources seemed to affect certain metabolites differently.