Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis-like cell death

Abstract

As a main element in the hard metal industry, cobalt is one of the major components of human metal implants. Cobalt-containing implants, especially joint prostheses used for artificial joint replacement, can be corroded due to the complex physiological environment in vivo, producing a large number of nanoscale cobalt particles (Cobalt Nanoparticles, CoNPs). These CoNPs can be first accumulated around the implant to cause adverse local reactions and then enter into the blood vessels followed by reaching the liver, heart, brain, kidney, and other organs through systematic circulation, which leads to multi-system toxicity symptoms. To ensure the long-term existence of cobalt-containing implants in the body, it is urgently required to find out a safe and effective detoxification drug. Herein, we have demonstrated that CoNPs could induce the ferroptosis-like cell death through the enhancement of intracellular reactive oxygen species (ROS) level, cytoplasmic Fe2+ level, lipid peroxidation, and consumption of reduced glutathione (GSH) as well as inhibition of glutathione peroxidase 4 (GPX4) activity. Importantly, α-lipoic acid (ALA), a natural antioxidant with the capability to scavenge free radicals and chelate toxic metals, was found to efficiently alleviate the adverse effects of CoNPs. The present study illustrates a new mechanism of CoNPs mediated by ferroptosis-like cytotoxicity and discloses an effective method for the detoxification of CoNPs by employing the natural antioxidant of ALA, providing a basis for further in vivo detoxification study.

In Sickness and in Health: The Oxygen Reactive Species and the Bone

“…In turn, the lower pH associated with inflammation is a contributor to corrosion phenomena; the resulting increase in released particles will perpetuate inflammation, further implant structural damage, and eventually promote systemic effects ( Eliaz, 2019 ; Hameister et al, 2020 ). Ferroptosis is a form of controlled cell death that occurs in the presence of iron overload and leads to the formation of lipid ROS ( Sharma and Flora, 2021 ), and its association with peri-implant inflammation and cell death has been suggested ( Liu et al, 2020 ). Likewise, increased local ROS levels, inflammation and metallosis have been associated with titanium alloy implants and tribocorrosion phenomena ( Borys et al, 2019 ; Eliaz, 2019 ).…”

Ferroptosis inhibitor alleviates cytotoxicity induced by cobalt nanoparticles through reactive oxygen species attenuation

“…The excessive accumulation of ROS and the production of a large number of in ammatory cytokines such as TNF-α play an important role in the toxicity mechanism induced by cobalt nanoparticles, leading to in ammation, cell damage and proliferation, which in turn leads to DNA damage and DNA mutations, as well as damage to mitochondria, lysosomes and the nucleus, eventually leading to cell death. Past studies have found that although the apoptosis rate of treatment is signi cantly higher than that of the control group, it is still much lower than the cell death rate [28]. Therefore, it could be possible that there are still other types of cell death besides apoptosis in MG-63 cells exposed to CoNPs.…”

Fluorescent CQD-Doped Styrene Acrylic Emulsion Coating Film with Enhanced Optical Properties

“…The appearance of abundant blue fluorescent aggregations was due to the absorbability of the CQDs, which could attract and enwrap neighboring particles. With the increasing CQD content, the blue fluorescence became stronger and more disordered, revealing that the bright PL emission of the CQDs formed from wood processing residues originated from their inherent carbon core of band gaps and extrinsic surface defects [ 30 ].…”