Activation of NLRP3 inflammasome in hepatocytes after exposure to cobalt nanoparticles: The role of oxidative stress. (December 2020)

• Record Type: Journal Article
• Authors: Feng, Sisi; Zhang, Zhenyu; Mo, Yiqing; Tong, Ruirui; Zhong, Zexiang; Chen, Zhong; He, Dan; Wan, Rong; Gao, Meiqin; Mo, Yiqun; Zhang, Qunwei; Huang, Yang
• Is Part Of: Toxicology in vitro. Volume 69(2020)
• Publication Date: 2020-12
• Subjects: Cobalt nanoparticles (Nano-Co) -- NOD-like receptor protein 3 (NLRP3) inflammasome -- Oxidative stress -- Mitochondrial reactive oxygen species (mtROS); Nano-Co cobalt nanoparticles -- NLRP3 Nod-like receptor protein 3 -- ASC apoptotic speck-like protein containing CARD -- IL-1β interleukin-1β -- IL-18 interleukin-18 -- ROS reactive oxygen species -- mtROS mitochondrial reactive oxygen species -- NAC N-acetyl-L-cysteine -- TEMPO mito-TEMPO (2-(2, 2, 6, 6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.104967
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: With the increased use of nanomaterials and increased exposure of humans to various nanomaterials, the potential health effects of nanomaterials cannot be ignored. The hepatotoxicity of cobalt nanoparticles (Nano-Co) is largely unknown and the underlying mechanisms remain obscure. The purpose of this study was to exam the hepatotoxicity induced by Nano-Co and its potential mechanisms. Our results showed that exposure of human fetal hepatocytes L02 to Nano-Co caused a dose- and a time-dependent cytotoxicity. Besides the generation of reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS), exposure to Nano-Co also caused activation of NOD-like receptor protein 3 (NLRP3) inflammasome in hepatocytes. After silencing NLRP3, one component of NLRP3 inflammasome, expression by siRNA strategy, we found that upregulation of NLRP3-related proteins was abolished in hepatocytes exposed to Nano-Co. Using antioxidants to scavenge ROS and mtROS, we demonstrated that Nano-Co-induced mtROS generation was related to Nano-Co-induced NLRP3 inflammasome activation. Our findings demonstrated that Nano-Co exposure may promote intracellular oxidative stress damage, and mtROS may mediate the activation of NLRP3 inflammasome in hepatocytes exposed to Nano-Co, suggesting an important role of ROS/NLRP3 pathway in Nano-Co-induced hepatotoxicity. These results provide scientific insights into the hepatotoxicity of Nano-Co and a basis for the prevention and treatment of Nano-Co-induced cytotoxicity. Highlights: Exposure of hepatocytes to cobalt nanoparticles (Nano-Co) caused cell toxicity. Nano-Co caused ROS/mtROS generation and intracellular oxidative stress damage. Nano-Co caused NLRP3 inflammasome activation. Nano-Co-induced ROS/mtROS may be involved in NLRP3 inflammasome activation. ROS/NLRP3 pathway plays an important role in Nano-Co-induced hepatotoxicity.