Department of Orthopaedics, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, China.
Orthopaedic Laboratory, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.
J Nanobiotechnology. 2020 Oct 2;18(1):141. doi: 10.1186/s12951-020-00700-8.
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 Fe 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.
作为硬质合金工业的主要元素之一，钴是人体金属植入物的主要成分之一。含钴的植入物，特别是用于人工关节置换的关节假体，由于体内复杂的生理环境，可能会发生腐蚀，产生大量纳米级钴颗粒（Cobalt Nanoparticles，CoNPs）。这些 CoNPs 可以首先在植入物周围积累，引起不良反应，然后通过系统循环进入血管，随后到达肝脏、心脏、大脑、肾脏和其他器官，导致多系统毒性症状。为了确保含钴植入物在体内的长期存在，迫切需要找到一种安全有效的解毒药物。在这里，我们证明 CoNPs 可以通过增强细胞内活性氧（ROS）水平、细胞质 Fe 水平、脂质过氧化、还原型谷胱甘肽（GSH）消耗以及抑制谷胱甘肽过氧化物酶 4（GPX4）活性来诱导类铁死亡样细胞死亡。重要的是，α-硫辛酸（ALA），一种具有清除自由基和螯合有毒金属能力的天然抗氧化剂，被发现可以有效缓解 CoNPs 的不良影响。本研究阐明了 CoNPs 通过类铁死亡样细胞毒性介导的新机制，并揭示了通过天然抗氧化剂 ALA 对 CoNPs 进行解毒的有效方法，为进一步的体内解毒研究提供了依据。
