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

• DOI: 10.1186/s12951-020-00700-8
• Publication Date: 2020-10-02T12:03:02Z
• Authors: Yake Liu; Wenfeng Zhu; Dalong Ni; Zihua Zhou; Jin-hua Gu; Weinan Zhang; Huanjian Sun; Fan Liu
• Keywords: Detoxification; Alpha-Lipoic Acid

Abstract As a main element in the hard metal industry, cobalt is one of major components human implants. Cobalt-containing implants, especially joint prostheses used for artificial replacement, can be corroded due to complex physiological environment vivo, producing large number nanoscale particles (Cobalt Nanoparticles, CoNPs). These CoNPs first accumulated around implant cause adverse local reactions and then enter into blood vessels followed by reaching liver, heart, brain, kidney, other organs through systematic circulation, which leads multi-system toxicity symptoms. To ensure long-term existence cobalt-containing implants body, it urgently required find out safe effective detoxification drug. Herein, we have demonstrated that could induce ferroptosis-like cell death enhancement intracellular reactive oxygen species (ROS) level, cytoplasmic Fe 2+ lipid peroxidation, consumption reduced glutathione (GSH) as well inhibition peroxidase 4 (GPX4) activity. Importantly, α-lipoic acid (ALA), natural antioxidant with capability scavenge free radicals chelate toxic metals, was found efficiently alleviate effects CoNPs. The present study illustrates new mechanism mediated cytotoxicity discloses an method employing ALA, providing basis further vivo study.