In vivo and in vitro toxicity of cobalt in the heart

Sarunya Laovitthayanggoon, Catherine J. Henderson, Rothwelle J. Tate, Susan Currie, Claire McCluskey, Margaret Macdonald, M. Helen Grant

Research output: Contribution to conferenceAbstract

Abstract

Wear debris from cobalt/chromium (Co/Cr) alloy metal-on-metal bearings in prosthetic hip replacements has created a significant internal source of cobalt exposure in these patients. Co toxicity is suspected to contribute to severe systemic adverse effects, including cardiac and CNS effects, in patients with high circulating Co concentrations. This study investigated the effects of chronic Co exposure to rats (1mg/kg i.p. CoCl2, daily, for 28 days) and Co uptake into primary adult rat cardiac fibroblasts (CFs). Co treatment was associated with accumulation into various organs of the body and significant increases in Co levels were detected in liver, kidney and heart. Echocardiography showed functional changes that correlated with compromised cardiac contractility. Fractional shortening was significantly reduced in CoCl2-treated rats following 28 days treatment compared to the control group (54.01±0.90% and 60.29±0.53% respectively), providing evidence of contractile dysfunction. Cellular studies examined uptake of CoCl2 into both CFs and 3T3 fibroblasts using inductively coupled plasma mass spectrometry (ICP-MS) to measure intracellular metal content. The range of Co uptake increased proportionally (0-50 µg/L) for the 3T3 cells, as well as for the CFs (about 0-120 µg/L) when the CoCl2 concentration in the medium was increased between 0 and 72 mg/L. Uptake of Co into CFs was significantly greater than into 3T3 cells. The greater accumulation of CoCl2 into CFs suggests Co ions in vivo could accumulate in these cells, leading to functional consequences on cardiac performance. Future work will focus on determining the underlying uptake mechanism which could have important therapeutic implications.

Conference

ConferenceBritish Toxicology Society Congress 2017
CountryUnited Kingdom
CityLiverpool
Period3/04/175/04/17
Internet address

Fingerprint

Fibroblasts
Toxicity
Cobalt
Rats
Bearings (structural)
Metals
Echocardiography
Cobalt alloys
Inductively coupled plasma mass spectrometry
Chromium alloys
Prosthetics
Debris
Liver
Wear of materials
Ions

Keywords

  • prosthetics
  • hip replacements
  • cobalt exposure

Cite this

Laovitthayanggoon, S., Henderson, C. J., Tate, R. J., Currie, S., McCluskey, C., Macdonald, M., & Grant, M. H. (2017). In vivo and in vitro toxicity of cobalt in the heart. Abstract from British Toxicology Society Congress 2017, Liverpool, United Kingdom.
Laovitthayanggoon, Sarunya ; Henderson, Catherine J. ; Tate, Rothwelle J. ; Currie, Susan ; McCluskey, Claire ; Macdonald, Margaret ; Grant, M. Helen. / In vivo and in vitro toxicity of cobalt in the heart. Abstract from British Toxicology Society Congress 2017, Liverpool, United Kingdom.1 p.
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abstract = "Wear debris from cobalt/chromium (Co/Cr) alloy metal-on-metal bearings in prosthetic hip replacements has created a significant internal source of cobalt exposure in these patients. Co toxicity is suspected to contribute to severe systemic adverse effects, including cardiac and CNS effects, in patients with high circulating Co concentrations. This study investigated the effects of chronic Co exposure to rats (1mg/kg i.p. CoCl2, daily, for 28 days) and Co uptake into primary adult rat cardiac fibroblasts (CFs). Co treatment was associated with accumulation into various organs of the body and significant increases in Co levels were detected in liver, kidney and heart. Echocardiography showed functional changes that correlated with compromised cardiac contractility. Fractional shortening was significantly reduced in CoCl2-treated rats following 28 days treatment compared to the control group (54.01±0.90{\%} and 60.29±0.53{\%} respectively), providing evidence of contractile dysfunction. Cellular studies examined uptake of CoCl2 into both CFs and 3T3 fibroblasts using inductively coupled plasma mass spectrometry (ICP-MS) to measure intracellular metal content. The range of Co uptake increased proportionally (0-50 µg/L) for the 3T3 cells, as well as for the CFs (about 0-120 µg/L) when the CoCl2 concentration in the medium was increased between 0 and 72 mg/L. Uptake of Co into CFs was significantly greater than into 3T3 cells. The greater accumulation of CoCl2 into CFs suggests Co ions in vivo could accumulate in these cells, leading to functional consequences on cardiac performance. Future work will focus on determining the underlying uptake mechanism which could have important therapeutic implications.",
keywords = "prosthetics, hip replacements, cobalt exposure",
author = "Sarunya Laovitthayanggoon and Henderson, {Catherine J.} and Tate, {Rothwelle J.} and Susan Currie and Claire McCluskey and Margaret Macdonald and Grant, {M. Helen}",
year = "2017",
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day = "3",
language = "English",
note = "British Toxicology Society Congress 2017 ; Conference date: 03-04-2017 Through 05-04-2017",
url = "http://www.thebts.org/bts-annual-congress-2017/",

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Laovitthayanggoon, S, Henderson, CJ, Tate, RJ, Currie, S, McCluskey, C, Macdonald, M & Grant, MH 2017, 'In vivo and in vitro toxicity of cobalt in the heart' British Toxicology Society Congress 2017, Liverpool, United Kingdom, 3/04/17 - 5/04/17, .

In vivo and in vitro toxicity of cobalt in the heart. / Laovitthayanggoon, Sarunya; Henderson, Catherine J.; Tate, Rothwelle J.; Currie, Susan; McCluskey, Claire; Macdonald, Margaret; Grant, M. Helen.

2017. Abstract from British Toxicology Society Congress 2017, Liverpool, United Kingdom.

Research output: Contribution to conferenceAbstract

TY - CONF

T1 - In vivo and in vitro toxicity of cobalt in the heart

AU - Laovitthayanggoon, Sarunya

AU - Henderson, Catherine J.

AU - Tate, Rothwelle J.

AU - Currie, Susan

AU - McCluskey, Claire

AU - Macdonald, Margaret

AU - Grant, M. Helen

PY - 2017/4/3

Y1 - 2017/4/3

N2 - Wear debris from cobalt/chromium (Co/Cr) alloy metal-on-metal bearings in prosthetic hip replacements has created a significant internal source of cobalt exposure in these patients. Co toxicity is suspected to contribute to severe systemic adverse effects, including cardiac and CNS effects, in patients with high circulating Co concentrations. This study investigated the effects of chronic Co exposure to rats (1mg/kg i.p. CoCl2, daily, for 28 days) and Co uptake into primary adult rat cardiac fibroblasts (CFs). Co treatment was associated with accumulation into various organs of the body and significant increases in Co levels were detected in liver, kidney and heart. Echocardiography showed functional changes that correlated with compromised cardiac contractility. Fractional shortening was significantly reduced in CoCl2-treated rats following 28 days treatment compared to the control group (54.01±0.90% and 60.29±0.53% respectively), providing evidence of contractile dysfunction. Cellular studies examined uptake of CoCl2 into both CFs and 3T3 fibroblasts using inductively coupled plasma mass spectrometry (ICP-MS) to measure intracellular metal content. The range of Co uptake increased proportionally (0-50 µg/L) for the 3T3 cells, as well as for the CFs (about 0-120 µg/L) when the CoCl2 concentration in the medium was increased between 0 and 72 mg/L. Uptake of Co into CFs was significantly greater than into 3T3 cells. The greater accumulation of CoCl2 into CFs suggests Co ions in vivo could accumulate in these cells, leading to functional consequences on cardiac performance. Future work will focus on determining the underlying uptake mechanism which could have important therapeutic implications.

AB - Wear debris from cobalt/chromium (Co/Cr) alloy metal-on-metal bearings in prosthetic hip replacements has created a significant internal source of cobalt exposure in these patients. Co toxicity is suspected to contribute to severe systemic adverse effects, including cardiac and CNS effects, in patients with high circulating Co concentrations. This study investigated the effects of chronic Co exposure to rats (1mg/kg i.p. CoCl2, daily, for 28 days) and Co uptake into primary adult rat cardiac fibroblasts (CFs). Co treatment was associated with accumulation into various organs of the body and significant increases in Co levels were detected in liver, kidney and heart. Echocardiography showed functional changes that correlated with compromised cardiac contractility. Fractional shortening was significantly reduced in CoCl2-treated rats following 28 days treatment compared to the control group (54.01±0.90% and 60.29±0.53% respectively), providing evidence of contractile dysfunction. Cellular studies examined uptake of CoCl2 into both CFs and 3T3 fibroblasts using inductively coupled plasma mass spectrometry (ICP-MS) to measure intracellular metal content. The range of Co uptake increased proportionally (0-50 µg/L) for the 3T3 cells, as well as for the CFs (about 0-120 µg/L) when the CoCl2 concentration in the medium was increased between 0 and 72 mg/L. Uptake of Co into CFs was significantly greater than into 3T3 cells. The greater accumulation of CoCl2 into CFs suggests Co ions in vivo could accumulate in these cells, leading to functional consequences on cardiac performance. Future work will focus on determining the underlying uptake mechanism which could have important therapeutic implications.

KW - prosthetics

KW - hip replacements

KW - cobalt exposure

UR - http://www.thebts.org/bts-annual-congress-2017/

M3 - Abstract

ER -

Laovitthayanggoon S, Henderson CJ, Tate RJ, Currie S, McCluskey C, Macdonald M et al. In vivo and in vitro toxicity of cobalt in the heart. 2017. Abstract from British Toxicology Society Congress 2017, Liverpool, United Kingdom.