Blood distribution of nickel, cobalt, and chromium following intramuscular injection into hamsters (original) (raw)
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Elimination of nickel, cobalt, and chromium following repeated injections of high dose metal salts
Journal of Biomedical Materials Research, 1989
A study was conducted to determine the ability of hamsters to eliminate in the urine, or store in the organs, large quantities of metal salts given over a period of several months. In addition, the effect of prior immunization on metal ion clearance was determined. The results indicated that nickel was rapidly eliminated in the urine and that the level in the organs was similar to that of control animals. Cobalt was eliminated more slowly than was nickel. The organ levels of cobalt were similar to those of control animals with a slight elevation in the liver of the injected animals. Chromium was eliminated in the urine very slowly, was red cell associated, and the levels were elevated in all the organs (liver, lung, spleen, kidney) compared to control. Prior immunization with metal salts increased the storage of chromium.
Comparison of cobalt and chromium binding to blood elements
Toxicology, 1984
Macromolecular binding of metals is thought to be a prerequisite for induction of metal sensitivity. In this study, the binding of cobalt(II) to blood components was investigated. Incubation of 6°Co with blood yielded a mean erythrocyte binding of 10.3 × 107 Co atoms/cell. Incubation of the metal with serum resulted in binding of 8.3 × 10-9 tool Co/rag protein. A comparison was made with analogous binding of chromium(III), a metal recognized for its sensitizing potency. Binding of chromium to proteins and blood cells was 20-fold higher than that obtained with cobalt. With both metals, binding to serum proteins was non-specific. The greater binding by chromium, when compared with cobalt, is consistent with the greater sensitizing ability of this metal.
In vitro andin vivo metal ion release
Journal of Biomedical Materials Research, 1988
A series of experiments was conducted to study in vitro and in vivo metal ion release and the urine excretion of metal ions. Metal salts were injected and urine analyzed. Anodic potentials were applied to stainless steel and cobalt-chromium-molybdenum (CCM) specimens to cause an acceleration of corrosion rates. Corrosion experiments were done in saline, 10% serum and in a subcutaneous space in hamsters. Corrosion rates were determined by measurements of weight loss and calculations of net charge transfer. Metal ion concentrations were determined with graphite furnace atomic absorption spectroscopy, and were calculated from total charge using Faraday's law. The results with stainless steel showed that the weight loss and metal ion release from stainless steel ii7 &ro and in vim can be calculated using Faraday's Law, assuming release in proportion to alloy composition. The results with CCM indicated that release rates in vifm can be used to determine the proportionality of release iri zlivo. All the nickel and most of the cobalt was rapidly excreted, while less than 50% of the chromium was excreted. The excretion of metals following salt injection or in oioo corrosion were very similar. INTRODUCTION A number of approaches have been taken to study corrosion and metal ion release from implants. Solid metal cylinders have been implanted in muscle in rabbits, and tissues and organs chemically analyzed for metal concen-tration~.'-~ These studies have demonstrated that metal ions are released and transported in vim. Black and co-workers4r5 have used metal powder in amounts corresponding to multiples of the surface area to body weight ratio of a total hip in a human. Their measurements of metal ion concentrations in blood components and urine have shown significant ion release, especially of nickel, which is not always in proportion to the alloy composition. Chemical analysis of tissues adjacent to implants in humans have also shown significant amounts of metal ions, especially chromium and titanium, which are not in proportion to alloy composition. 6-9 Chemical analysis of hair,"," serum,'2,L? and urine14-"j from animals and patients has also been performed as a way to determine release rates in zlivo. Chemical analysis of blood serum and cells have also demonstrated that chromium with a valence of + 6 is This paper was presented in part at the 12th Annual meeting of the Society for Bio
Materials …, 2010
Despite the interest in identifying systemic effects caused by the metallic particles released from long term metallic implants in the body, few works support reliable conclusions about the effects of those particles in organs. The aim of the present work is to look for damages in tissues of liver, kidney, lung and heart of rats submitted to injection of Hank's solution contained particles of Ti6Al4V alloy and Stainless Steel 316L, obtained by metal friction. The particles size ranges from 50 to 200 µm for the Ti alloy and from 100 to 500 µm for the 316L. Tissues isolated from the organs after the euthanasia were prepared and analyzed in an optical microscope and Energy Dispersive Spectrometer (EDS). Lesions caused by an inflammatory response such as strange body epithelioid granuloma and giant cells were found in some of the tissues containing yttrium and aluminum.
Organ damage by toxic metals is critically determined by the bloodstream
Coordination Chemistry Reviews, 2018
Past poisoning epidemics have revealed that the chronic exposure to exceedingly small daily doses of toxic metal and metalloid species can-over time-severely affect human health. Today, several potentially toxic metals and metalloids have been accurately quantified in the bloodstream of the average population, but the interpretation of these from a public health point of view remains problematic. Conversely, the biomolecular origin for a multitude of grievous human diseases remains unknown. Supported by recent epidemiological evidence, these seemingly unrelated facts suggest that human exposure to the aforementioned pollutants may be linked to the etiology of more adverse health effects than we currently know. Based on the interaction of toxic metal and metalloid species with essential trace elements, plasma and erythrocytes in the bloodstream, we have previously argued that a better understanding of these bioinorganic chemistry processes are destined to provide important new insight into their mechanisms of chronic toxicity. This perspective provides an update on recent advances to better understand these bioinorganic processes and attempts to integrate these findings with the whole organism in order to establish connections with the etiology of human diseases. Based on the recent observation of the arsenite-induced perturbation of the whole-body distribution of selenite in mammals and the mercuration of hemoglobin in erythrocyte cytosol it is argued that bioinorganic processes in the bloodstream critically determine which metal and/or non-metal containing species will impinge on the toxicological target organ(s). Accordingly, the bioinorganic chemistry that unfolds in the bloodstream represents a critical bottleneck in terms of linking the exposure of humans to toxic metal species with the etiology of diseases. Furthermore, a better understanding of the blood-based detoxification of environmentally abundant toxic metal species is of direct practical use to develop palliative treatments to ameliorate the adverse effect that toxic metal species exert on certain human populations.
Journal of Orthopaedic Research, 2012
Evidence shows that raised cobalt (Co), chromium (Cr), and nickel (Ni) whole blood concentrations correlate with poor device outcome in patients following metal-on-metal (MoM) hip arthroplasty. To understand the local and systemic pathological effects of these raised metal concentrations it is important to define their distribution between whole blood, plasma, and urine. The metals were measured by Inductively Coupled Plasma Mass Spectrometry (ICPMS). Two hundred and five plasma, 199 whole blood, and 24 sets of urine samples were analyzed from 202 patients with Co-Cr alloy MoM hip prostheses implanted between 8 months to 12 years (mean 6.0 years) prior to analysis. Plasma Co (median 39.1 nmol/L) showed significantly positive 1:1 correlation with whole blood Co (median 45.9 nmol/L; R 2 ¼ 0.98, p < 0.001, slope ¼ 1.0). Plasma Cr (median 53.8 nmol/L) and whole blood Cr (median 40.3 nmol/L) were also correlated; however, concentrations were significantly higher in plasma indicating relatively little blood cell uptake (R 2 ¼ 0.96, p < 0.001, slope ¼ 1.6). Urinary Co was up to threefold higher than Cr (median 334.0 vs. 97.3 nmol/L respectively). Nickel concentrations in whole blood, plasma, and urine were low relative to Co and Cr. The analysis shows fundamental differences in the physiological handling of these metals: Co is distributed approximately equally between blood cells and plasma, whereas Cr is mainly in plasma, despite which, Cr had far less renal excretion than Co.
Toxicology Reports, 2021
Background: Wounds with embedded metal fragments are an unfortunate consequence of armed conflicts. In many cases the exact identity of the metal(s) and their long-term health effects, especially on the kidney, are not known. Aim of study: The aim of this study was to quantitate the urinary levels of metals solubilized from surgically implanted metal pellets and to assess the effect of these metals on the kidney using a battery of biomarker assays. Materials and methods: Using a rodent model system developed in our Institute to simulate embedded fragment injuries, eight metals considered likely components of an embedded fragment wound were individually implanted into the gastrocnemius muscle of male Sprague-Dawley rats. The rats were followed for 12 months post-implantation with urine collected prior to surgery then at 1-, 3-, 6-, 9-, and 12-months post-implantation to provide a within-subjects cohort for examination. Urinary metal levels were determined using inductively coupled plasma-mass spectrometry and urinary biomarkers assessed using commercially available kits to determine metal-induced kidney effects. Results: With few exceptions, most of the implanted metals rapidly solubilized and were found in the urine at significantly higher levels than in control animals as early as 1-month post-implantation. Surprisingly, many of the biomarkers measured were decreased compared to control at 1-month post-implantation before returning to normal at the later time points. However, two metals, iron and depleted uranium, showed increased levels of several markers at later time points, yet these levels also returned to normal as time progressed. Conclusion: This study showed that metal pellets surgically implanted into the leg muscle of Sprague-Dawley rats rapidly solubilized with significant levels of the implanted metal found in the urine. Although kidney biomarker results were inconsistent, the changes observed along with the relatively low amounts of metal implanted, suggest that metal-induced renal effects need to be considered when caring for individuals with embedded metal fragment wounds.
Cytotoxic effects of cobalt and nickel ions on osteocytes in vitro
Journal of Orthopaedic Surgery and Research, 2014
Background: Metal-on-metal prostheses undergo wear and corrosion, releasing soluble ions and wear particles into the surrounding environment. Reports described early failures of the metal-on-metal prostheses, with histologic features similar to a Type IV immune response. Mechanisms by which metal wear products and metal ion causing this reaction are not completely understood, and the effects of metal ions on osteocytes, which represent more than 95% of all the bone cells, have not been also studied. We hypothesized that soluble metal ions released from the cobalt-chromiummolybdenum (Co-Cr-Mo) prosthesis may have cytotoxic effect on osteocytes. Methods: MLO-Y4 osteocytes were treated with various metal ion solutions for 24 and 48 h. The effect of ion treatment on cytotoxicity was assessed by WST-1 reagents and cell death ELISA. Morphological changes were analyzed by a phase-contrast microscope or fluorescent microscope using Hoechst 33342 and propidium iodine staining. Results: Cr and Mo ions did not cause cell death under 0.50 mM, highest concentration studied, whereas Co and Ni ions had significant cytotoxic effect on MLO-Y4 cells at concentrations grater than 0.10 mM and at 0.50 mM, respectively, in a dose-dependent manner. According to the ELISA data, osteocytes treated with Co ions were more susceptible to necrotic than apoptotic cell death, while Ni ions caused osteocyte apoptosis. The morphological assays show that cells treated with Co and Ni ions at high concentration were fewer in number and rounded. In addition, fluorescent images showed a marked reduction in live cells and an increase in dead osteocytes treated with Co and Ni ions at high concentration. Conclusions: Metal ions released from metal-on-metal bearing surfaces have potentially cytotoxic effects on MLO-Y4 osteocytes, in vitro.
Archives of Orthopaedic and Trauma Surgery, 2011
Introduction A patient with a total hip replacement developed optic, acoustic and peripheral neuropathy from metal ions intoxication, due to the wear products released from the prosthesis. Subsequently the kinetics of the metal ions was studied. Materials and methods Massive wear and acute intoxication allowed a study of the metal ions kinetics and of EDTA treatment. Results Plasma and other organic fluids were saturated by each of the metal ions released from the exposed surface according to the solubility of each ion; a larger fraction of Co ions was bound within red cells, while the plasmatic fraction appeared more movable. In a patient with a prosthesis subjected to wear, the ions released are from the prosthetic and from the debris surface (spread in the body). The latter is a function of the number and size of particles. Discussion Revision of the prosthesis from the point of view of the metal ions kinetics corresponded to a reduction of the releasing surface because of debris washed out by irrigation and tissue excision; however, the metal particles spread by lymphatic circulation continued to release ions even though the source of wear had been removed. Early diagnosis of high metal wear can be ascertained with mass spectrometry and after revision high levels of metal ions can only be reduced with repeated chelating treatment. It is preferable not to revise fractured ceramic components with a polyethylene-metal articulation.
Metal ions activate vascular endothelial cells and increase lymphocyte chemotaxis and binding
Journal of Orthopaedic Research, 2013
Metal on metal articulations in hip arthroplasty offer advantages, including lower volumetric wear compared to conventional metalonpolyethylene bearings, and increased resistance to dislocation. Reports described early failures, with histologic features similar to a Type IV immune response. Mechanisms by which metal wear products cause this reaction are not completely understood. We hypothesized a mechanism through direct activation of endothelial cells (ECs) by metal ions, resulting in both vasculitis and accumulation of lymphocytes without prior immune sensitization. Effects of metal ions were evaluated using human ECs in culture. Alterations in chemotactic proteins IL8 and MCP1 were assessed, as was upregulation of the adhesion molecule ICAM-1 and lymphocyte binding to ECs. Cobalt increased secretion of IL8 and MCP1 significantly, and upregulated the expression of ICAM-1 in ECs compared to stimulation by chromium and controls. Binding of lymphocytes to ECs and transEC migration were both significantly increased by cobalt but not chromium. These findings suggest that cobalt contributes more to the activation of ECs and lymphocyte binding than chromium without an allergic response. Some of the adverse tissue reactions to implants with components made of cobalt-chromium-molybdenium alloys may be due in part to activation of the endothelium by metal ions. ß