The Protective Effect of Bafilomycin A1 Against Cobalt Nanoparticle-Induced Cytotoxicity and Aseptic Inflammation in Macrophages In Vitro

Abstract

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.

Liver Toxicity of Cadmium Telluride Quantum Dots (CdTe QDs) Due to Oxidative Stress in Vitro and in Vivo

“…Oxidative stress is currently believed to be the main modulator of adverse effects upon exposure to nanoparticles [ 13 , 27 , 28 , 29 ]. Previous studies have shown that exposure to nanoparticles could induce intracellular oxidative stress by disturbing the balance between the oxidant and antioxidant processes [ 30 ]. However, not much is known regarding the oxidative stress caused by QDs in vivo .…”

<p>Local Cellular Responses to Metallic and Ceramic Nanoparticles from Orthopedic Joint Arthroplasty Implants</p>

“…Interestingly, changing the acidic environment inside the lysosome using Bafilomycin A1 protects the viability of RAW264.7 cells and suppresses Co NP-induced aseptic inflammation by inhibiting intracellular Co NP corrosion and Co ions release. 102 The cytotoxic and inflammatory effects of Co NPs (28 nm) on macrophages were also observed by Nyga et al This effect is dependent on hypoxia-inducible factor (HIF), a ROS-independent pathway. 103 Notably, it is Co NPs, but not Cr NPs, which inhibit macrophage migration both in vitro and in vivo by promoting adhesion at non-cytotoxic concentrations; this is associated with ROS-RhoA signaling pathway.…”

Controlled and sustained drug release performance of calcium sulfate cement porous TiO₂ microsphere composites

“…In this range, it won't change body fluid environment (7-7.4) or induce aseptic inflammation, which is caused by a low pH value of the body fluid environment, can be avoided. 40 It is also relevant to bone metabolic pro-cess; a relatively low pH is ill-suited to bone metabolism and mineralization. 41 Morphology of composite cements during in vitro drug release Figure 7 shows the surface morphology and composition of composite cements.…”