title: Molecular analysis of chromium and cobalt-related toxicity.
abstract: Occupational and environmental exposure to Co and Cr has been previously linked to a wide array of inflammatory and degenerative conditions and cancer. Recently, significant health concerns have been raised by the high levels of Cr and Co ions and corrosion products released by biomedical implants. Herein, we set to analyze the biological responses associated with Co and Cr toxicity. Histological, ultrastructural, and elemental analysis, performed on Cr and Co exposed patients reveal the presence of corrosion products, metallic wear debris and metal ions at varying concentrations. Metallic ions and corrosion products were also generated in vitro following macrophage phagocytosis of metal alloys. Ex vivo redox proteomic mapped several oxidatively damaged proteins by Cr(III) and Co(II)-induced Fenton reaction. Importantly, a positive correlation between the tissue amounts of Cr(III) and Co(II) ions and tissue oxidative damage was observed. Immobilized- Cr(III) and Co(II) affinity chromatography indicated that metal ions can also directly bind to several metallo and non-metalloproteins and, as demonstrated for aldolase and catalase, induce loss of their biological function. Altogether, our analysis reveals several biological mechanisms leading to tissue damage, necrosis, and inflammation in patients with Cr and Co-associated adverse local tissue reactions.
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461.
authors.forename: Brian
authors.initials: B
authors.lastname: Scharf
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461.
authors.forename: Cristina C
authors.initials: CC
authors.lastname: Clement
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461.
authors.forename: Valerio
authors.initials: V
authors.lastname: Zolla
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Perino
authors.affiliation: Department of Chemistry, University of Massachusetts, Amherst, MA 01003.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Department of Chemistry, University of Massachusetts, Amherst, MA 01003.
authors.forename: S Gokhan
authors.initials: SG
authors.lastname: Elci
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021.
authors.forename: E
authors.initials: E
authors.lastname: Purdue
authors.affiliation: Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021.
authors.forename: S
authors.initials: S
authors.lastname: Goldring
authors.affiliation: Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461.
authors.forename: Frank
authors.initials: F
authors.lastname: Macaluso
authors.affiliation: Orthopaedic Surgery, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461.
authors.forename: Neil
authors.initials: N
authors.lastname: Cobelli
authors.affiliation: Department of Chemistry, University of Massachusetts, Amherst, MA 01003.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Vachet
authors.affiliation: 1] Department of Pathology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461 [2] Orthopaedic Surgery, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461 [3] Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461.
authors.forename: Laura
authors.initials: L
authors.lastname: Santambrogio
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D019644:Arthroplasty, Replacement, Hip; D002374:Catalase / Q000037:antagonists & inhibitors / Q000737:chemistry; D002478:Cells, Cultured; D002857:Chromium / Q000737:chemistry / Q000633:toxicity*; D003035:Cobalt / Q000737:chemistry / Q000633:toxicity*; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors / Q000737:chemistry; D006621:Hip Joint / Q000187:drug effects / Q000276:immunology; D006622:Hip Prosthesis; D006801:Humans; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D061825:Metal-on-Metal Joint Prostheses; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D018384:Oxidative Stress; D010587:Phagocytosis; D050050:Protein Carbonylation
chemical_list: D002857:Chromium; D003035:Cobalt; D002374:Catalase; D005634:Fructose-Bisphosphate Aldolase