Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis-like cell death
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Journal of Nanobiotechnology Open Access
RESEARCH
Alpha lipoic acid antagonizes cytotoxicity of cobalt nanoparticles by inhibiting ferroptosis‑like cell death Yake Liu1,2†, Wenfeng Zhu1,5†, Dalong Ni3, Zihua Zhou2, Jin‑hua Gu4, Weinan Zhang1,2, Huanjian Sun5 and Fan Liu1*
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 Nano‑ particles, 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 dem‑ onstrated 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, pro‑ viding a basis for further in vivo detoxification study. Keywords: Cobalt nanoparticles, Nanotoxicity, Ferroptosis, Alpha-lipoic acid, Detoxification Introduction Hard metal is an alloy based on tungsten carbide (WC) and cobalt (Co), which is the key component of the joint prosthesis for artificial joint replacement. When an artificial joint is implanted in the body, degradation of the prosthesis is inevitable due to different physical and chemical effects such as mechanical stress, fretting, or fatigue corrosion, leading to the generation of metal particles with different diameters. Among these particles, *Correspondence: [email protected] † Yake Liu and Wenfeng Zhu contributed equally to this work 1 Department of Orthopaedics, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu, China Full list of author information is available at the end of the article
cobalt nanoparticles (CoNPs) are the most abundant ones with the highest toxicity [1, 2], which could cause early failure of artificial joints [3]. Tower et al. well demonstrated the multiple systemic adverse reactions after metal-on-metal (MOM) joint replacement and named the disease as arthroprosthetic cobaltism syndrome (ACS) [4–8]. CoNPs produced by th
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