title: Cobalt-chromium-molybdenum alloy causes metal accumulation and metallothionein up-regulation in rat liver and kidney.
abstract: Cobalt-chromium-molybdenum (CoCrMo) metal-on-metal hip prosthesis has had a revival due to their excellent wear properties. However, particulate wear debris and metal ions liberated from the CoCrMo alloys might cause carcinogenicity, hypersensitivity, local and general tissue toxicity, genotoxicity and inflammation-generating qualities. Nine months after implanting small pieces of CoCrMo alloy intramuscularly and intraperitoneally in rats, we analysed the accumulation of metals with a multi-element analysis, and the levels of metallothionein I/II with real-time reverse transcriptase-polymerase chain reaction in liver and kidney. We found that metal ions are liberated from CoCrMo alloys and suggest that they are released by dissolucytosis, a process where macrophages causes the metallic surface to release metal ions. Animals with intramuscular implants accumulated metal in liver and kidney and metallohionein I/II were elevated in liver tissue. The present data do not tell whether kidney and liver are the primary target organs or what possible toxicological effect the different metal ions might have, but they show that metal ions are liberated from CoCrMo alloys that are not subjected to mechanical wear and that they accumulate in liver and kidney tissue. That the liberated metal ions affect the tissues is supported by an up-regulation of the detoxifying/pacifying metalloprotein I/II in the liver.
authors.affiliation: Department of Neurobiology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark. Stig.Jakobsen@ki.au.dk
authors.forename: Stig S
authors.initials: SS
authors.lastname: Jakobsen
authors.forename: Gorm
authors.initials: G
authors.lastname: Danscher
authors.forename: Meredin
authors.initials: M
authors.lastname: Stoltenberg
authors.forename: Agnete
authors.initials: A
authors.lastname: Larsen
authors.forename: Jens M
authors.initials: JM
authors.lastname: Bruun
authors.forename: Tina
authors.initials: T
authors.lastname: Mygind
authors.forename: Kaare
authors.initials: K
authors.lastname: Kemp
authors.forename: Kjeld
authors.initials: K
authors.lastname: Soballe
mesh_terms: D000818:Animals; D002858:Chromium Alloys / Q000493:pharmacokinetics / Q000494:pharmacology*; D003035:Cobalt / Q000493:pharmacokinetics / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000187:drug effects* / Q000378:metabolism; D008982:Molybdenum / Q000493:pharmacokinetics / Q000494:pharmacology*; D019736:Prostheses and Implants; D012333:RNA, Messenger; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D002858:Chromium Alloys; D012333:RNA, Messenger; D003035:Cobalt; D008982:Molybdenum; D008668:Metallothionein