Co
ions released due to corrosion of Co nanoparticles (CoNPs) in the lysosomes of macrophages may be
a factor in the particle-induced cytotoxicity and aseptic
inflammation accompanying
metal-on-
metal (MOM)
hip prosthesis failure. Here, we show that CoNPs are easily dissolved under a low pH, simulating the acidic lysosomal environment. We then used
bafilomycin A1 to change the pH inside the lysosome to inhibit intracellular corrosion of CoNPs and then investigated its protective effects against CoNP-induced cytotoxicity and aseptic
inflammation on murine macrophage RAW264.7 cells. XTT {2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonyl]-2H-tetrazolium
hydroxide} assays revealed that
bafilomycin A1 can significantly decrease CoNP-induced cytotoxicity in RAW264.7 cells.
Enzyme-linked
immunosorbent assays showed that
bafilomycin A1 can significantly decrease the subtoxic concentration of CoNP-induced levels of pro-inflammatory
cytokines (
tumor necrosis factor-α,
interleukin-1β, and
interleukin-6), but has no effect on anti-inflammatory
cytokines (
transforming growth factor-β and
interleukin-10) in RAW264.7 cells. We studied the protective mechanism of
bafilomycin A1 against CoNP-induced effects in RAW264.7 cells by measuring
glutathione/oxidized glutathione (GSH/
GSSG),
superoxide dismutase,
catalase, and
glutathione peroxidase levels and employed scanning electron microscopy, transmission electron microscopy, and energy dispersive spectrometer assays to observe the ultrastructural cellular changes. The changes associated with apoptosis were assessed by examining the pAKT and cleaved
caspase-3 levels using Western blotting. These data strongly suggested that
bafilomycin A1 can potentially suppress CoNP-induced cytotoxicity and aseptic
inflammation by inhibiting intracellular corrosion of CoNPs and that the reduction in Co
ions released from CoNPs may play an important role in downregulating oxidative stress in RAW264.7 cells.