Molecular analysis of chromium and cobalt-related toxicity

• Published in: Scientific reports 2014-07, Vol.4 (1), p.5729, Article 5729
• Main Authors: Scharf, Brian, Clement, Cristina C., Zolla, Valerio, Perino, Giorgio, Yan, Bo, Elci, S. Gokhan, Purdue, E., Goldring, S., Macaluso, Frank, Cobelli, Neil, Vachet, Richard W., Santambrogio, Laura
• Format: Article
• Language: English
• Subjects: 13; 692/1537; 692/1537/805; 82; 82/58; Adult; Affinity chromatography; Aged; Aged, 80 and over; Alloys; Animals; Arthroplasty, Replacement, Hip; Cancer; Catalase; Catalase - antagonists & inhibitors; Catalase - chemistry; Cells, Cultured; Chromium; Chromium - chemistry; Chromium - toxicity; Cobalt; Cobalt - chemistry; Cobalt - toxicity; Corrosion; Female; Fructose-Bisphosphate Aldolase - antagonists & inhibitors; Fructose-Bisphosphate Aldolase - chemistry; Hip Joint - drug effects; Hip Joint - immunology; Hip Prosthesis; Humanities and Social Sciences; Humans; Inflammation; Ions; Macrophages; Male; Metal concentrations; Metal ions; Metal Nanoparticles - chemistry; Metal Nanoparticles - toxicity; Metal-on-Metal Joint Prostheses; Mice, Inbred C57BL; Middle Aged; multidisciplinary; Occupational exposure; Oxidative Stress; Particulate matter; Phagocytosis; Protein Carbonylation; Science; Toxicity
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep05729

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.