CdSe/ZnS quantum dots induce hepatocyte pyroptosis and liver inflammation via NLRP3 inflammasome activation. (June 2016)

• Record Type: Journal Article
• Authors: Lu, Yonghui; Xu, Shangcheng; Chen, Haiyan; He, Mindi; Deng, Youcai; Cao, Zhengwang; Pi, Huifeng; Chen, Chunhai; Li, Min; Ma, Qinlong; Gao, Peng; Ji, Yan; Zhang, Lei; Yu, Zhengping; Zhou, Zhou
• Is Part Of: Biomaterials. Volume 90(2016)
• Page Start: 27
• Page End: 39
• Publication Date: 2016-06
• Subjects: Quantum dots -- Hepatocyte pyroptosis -- Liver inflammation -- NLRP3 -- Reactive oxygen species -- Calcium mobilization; QDs quantum dots -- NLRP3 NLR pyrin domain containing 3 -- mtROS mitochondrial reactive oxygen species -- ASC apoptotic speck-like protein containing CARD -- IL-1β interleukin-1β -- PAMPs pathogen-associated molecular patterns -- DAMPs danger-associated molecular patterns -- TEM transmission electron microscopy -- NAC N-acetyl-l-cysteine -- 2-APB 2-aminoethoxydiphenyl borate -- NLRP3 KO NLRP3 knockout -- LDH lactate dehydrogenase -- TNF-α tumor necrosis factor-α -- siRNA small interfering RNA -- HBSS Hanks balanced salt solution -- WT wild-type -- Casp1 p20 caspase-1 p20 -- pro-Casp1 pro-caspase-1 -- FCM flow cytometry -- mRNA messenger RNA -- MPO myeloperoxidase -- CXCL1 chemokine [C-X-C motif] ligand 1 -- ALP alkaline phosphatase -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- YVAD Z-YVAD-FMK -- TEMPO Mito-TEMPO -- H&E hematoxylin and eosin -- γGT γ-glutamyltransferase; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2016.03.003
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Increased biomedical applications of quantum dots (QDs) have raised considerable concern regarding their toxicological impact. However, the toxicity of QDs is largely unknown and the underlying mechanism is still undefined. This study was conducted to examine the hepatotoxicity of CdSe/ZnS core/shell QDs and the underlying mechanism. In hepatic L02 cells, the QDs caused cytotoxicity in a dose-dependent manner. The QDs were then shown to activate the NLR pyrin domain containing 3 (NLRP3) inflammasome in hepatocytes, leading to a novel pro-inflammatory form of cell death named pyroptosis. Further experiments demonstrated that the QDs induced mitochondrial reactive oxygen species (mtROS) production, and that both a mtROS and a total ROS scavenger attenuated QDs-induced NLRP3 activation and pyroptosis. In addition, QDs increased cytoplasmic calcium (Ca 2+ ) levels, while a Ca 2+ release antagonist and chelator alleviated QDs-induced mtROS, NLRP3 activation and subsequent pyroptosis in hepatocytes. In vivo, QDs administration induced liver inflammation and dysfunction. Moreover, the QDs also resulted in NLRP3 activation in liver tissue. However, QDs-induced liver inflammation and dysfunction were abolished in NLRP3 knockout mice. Also, an elevation in mtROS was observed in liver after QDs administration, and the mtROS scavenger suppressed liver NLRP3 activation, inflammation and dysfunction induced by QDs. Our data suggest that QDs induced hepatocyte pyroptosis, liver inflammation and dysfunction via NLRP3 activation, which was caused by QDs-triggered mtROS production and Ca 2+ mobilization. Our results provide novel insights into QDs-induced hepatotoxicity and the underlying mechanism, facilitating control of the side effects of QDs.