Effects of cobalt and chromium ions on oxidative stress and energy metabolism in macrophages in vitro

Cobalt and chromium ions released from cobalt-chromium-molybdenum (CoCrMo)-based implants are a potential health concern, especially since both ions have been shown to induce oxidative stress in macrophages, the predominant immune cells in periprosthetic tissues. Ions of other transition metals (Cd, Ni) have been reported to inhibit the activity of mitochondrial enzymes in the electron transport chain. However, the effects of Co and Cr ions on the energy metabolism of macrophages remain largely unknown. The objective of the present study was to analyze the effects of Co2+ and Cr3+ on oxidative stress and energy metabolism in macrophages in vitro. RAW 264.7 murine macrophages were exposed to 6-18 ppm Co2+ or 50-150 ppm Cr3+. Results showed a significant increase in two markers of oxidative stress, reactive oxygen species level and protein carbonyl content, with increasing concentrations of Co2+, but not with Cr3+. In addition, oxygen consumption rates (OCR; measured using an extracellular flux analyzer) showed significant decreases in both mitochondrial respiration and non-mitochondrial oxygen consumption with increasing concentrations of Co2+, but not with Cr3+. OCR results further showed that Co2+, but not Cr3+, induced mitochondrial dysfunction, including a decrease in oxidative phosphorylation capacity. Overall, this study suggests that mitochondrial dysfunction may contribute to Co2+-induced oxidative stress in macrophages, and thereby to the inflammatory response observed in periprosthetic tissues. (c) 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3178-3187, 2018.