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CdSe/ZnS quantum dots induce hepatocyte pyroptosis and liver inflammation via NLRP3 inflammasome activation

Paper ID Volume ID Publish Year Pages File Format Full-Text
5391 372 2016 13 PDF Available
Title
CdSe/ZnS quantum dots induce hepatocyte pyroptosis and liver inflammation via NLRP3 inflammasome activation
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 (Ca2+) levels, while a Ca2+ 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 Ca2+ mobilization. Our results provide novel insights into QDs-induced hepatotoxicity and the underlying mechanism, facilitating control of the side effects of QDs.

Keywords
Quantum dots; Hepatocyte pyroptosis; Liver inflammation; NLRP3; Reactive oxygen species; Calcium mobilizationQDs, quantum dots; NLRP3, NLR pyrin domain containing 3; mtROS, mitochondrial reactive oxygen species; ASC, apoptotic speck-like protein containin
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CdSe/ZnS quantum dots induce hepatocyte pyroptosis and liver inflammation via NLRP3 inflammasome activation
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 90, June 2016, Pages 27–39
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us