The effect of ascorbic acid on the distribution of soluble Cr and Co ions in the blood and organs of rats.

Metal ions (Cr and Co) are released from metal orthopaedic implants in situ. We investigated tissue dissemination of Cr III, Cr VI and Co II ions in the body, and determined if administration of ascorbic acid (AA) affected their in vivo distribution using rats as a model system. Organs of rats treated with both Cr (VI) and Co (II) have higher metal ion levels when compared with control levels in the organs of rats without metal treatment. The reduced form of chromium, Cr III, is reported to be relatively impermeant to cell membranes in vitro, and in line with this, Cr III did not distribute into the organs of the rats after administration in vivo. Potent in vitro reduction of Cr (VI) to Cr III by AA was observed in this study. Prior intraperitoneal injection of AA lowered tissue uptake of both Cr VI and Co II, and increased faecal excretion, but not to a significant extent. AA may only be effective in increasing elimination of Cr VI at high concentrations when plasma reduction is saturated, and may be of limited therapeutic use in patients with orthopaedic implants.

Distribution of metal released from cobalt-chromium alloy orthopaedic wear particles implanted into air pouches in mice.

Metal-on-metal hip replacement implants generate wear debris and release ions both locally and systemically in patients. To investigate dissemination of metal, we determined blood and organ levels of cobalt (Co), chromium (Cr), and molybdenum (Mo) following the implantation of Co-Cr alloy wear debris in mice using skin pouches as a model system. We observed increased metal levels in blood for up to 72 h; the levels of Co were highest and remained elevated for 7 days. Co levels were elevated in all organs studied (liver, kidney, spleen, lung, heart, brain, and testes), with the peak at 48 h; highest levels were measured in liver and kidney (838.9 ± 223.7 ng/g in liver, and 938.8 ± 131.6 ng/g in kidney). Organ Cr levels were considerably lower than Co levels, for example, Cr in kidney was 117.2 ± 12.6 ng/g tissue at 48 h. Co is more mobile than Cr, reaching higher levels at earlier time points. This could be due to local tissue binding of Cr. Exposure to Co-Cr particles in vivo altered antioxidant enzyme expression and activities. We observed induction of catalase protein in the liver and glutathione reductase (GR) and peroxidase (GPx) proteins in the spleen. Activities of catalase and GPx in the liver were significantly increased while that of GR was decreased in the kidney. Organs of mice with Co-Cr particle implantation were exposed to increased metal levels capable of inducing reactive oxygen species scavenging enzymes, suggesting the tissue may be subjected to oxidative stress; however, the overall antioxidant defence system was not markedly disturbed.

Effect of chromium and cobalt ions on phase I and phase II enzymatic activities in vitro in freshly isolated rat hepatocytes.

The effect of in vitro exposure to the metal ions (chromium (VI) and cobalt (II)) on phase I and phase II enzymatic activities in freshly isolated rat hepatocytes is reported. Concentrations of metal ions used reflect those reported in the livers of cadavers that had worn metal-on-metal hip implants. To assess the effect of exposure to metal ions on enzymatic activities of phase I metabolic reactions the hydroxylations of testosterone were measured, and the phase II reactions measured were glucuronidation and sulfation. No effect was observed in the formation of the testosterone metabolites measured in the presence of either ion, Cr (VI) inhibited both glucuronidation and sulfation of 7-hydroxycoumarin (7-HC) and 1-naphthol, while Co inhibited only the glucuronidation of 7-HC and 1-naphthol. ATP levels were reduced in freshly isolated rat hepatocytes treated with Cr (VI) compared with control hepatocytes with no metal treatment. Cr (VI) probably inhibits the formation of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), the high energy co-factor of sulfation, by reducing the availability of ATP and also by acting as a substrate analog and competing with sulfate for ATP-sulfurylase. High concentrations of these metal ions in the livers of patients with loose or worn metal implants may act synergistically, and have consequences for the metabolism of xenobiotics.

The effect of anticoagulants on the distribution of chromium VI in blood fractions.

Metal-on-metal resurfacing arthroplasty is associated with elevated circulating levels of cobalt and chromium ions. To establish the long-term safety of metal-on-metal resurfacing arthroplasty, it has been recommended that during clinical follow-up of these patients, the levels of these metal ions in blood be monitored. In this article, we provide information on the distribution of chromium VI ions (the predominant form of chromium released by cobalt-chrome alloys in vivo and in vitro) in blood fractions. Chromium VI is predominantly partitioned into red blood cells compared with plasma (analysis of variance, P < .05). The extent of accumulation in red blood cells is influenced by the anticoagulant used to collect the blood, with EDTA giving a lower partitioning into red cells compared with sodium citrate and sodium heparin.