RRC ID 68974
Author Pang Y, Wu D, Ma Y, Cao Y, Liu Q, Tang M, Pu Y, Zhang T.
Title Reactive oxygen species trigger NF-κB-mediated NLRP3 inflammasome activation involvement in low-dose CdTe QDs exposure-induced hepatotoxicity.
Journal Redox Biol
Abstract Cadmium telluride (CdTe) quantum dots (QDs) can be employed as imaging and drug delivery tools; however, the toxic effects and mechanisms of low-dose exposure are unclear. Therefore, this pioneering study focused on hepatic macrophages (Kupffer cells, KCs) and explored the potential damage process induced by exposure to low-dose CdTe QDs. In vivo results showed that both 2.5 μM/kg·bw and 10 μM/kg·bw could both activate KCs to cause liver injury, and produce inflammation by disturbing antioxidant levels. Abnormal liver function further verified the risks of low-dose exposure to CdTe QDs. The KC model demonstrated that low-dose CdTe QDs (0 nM, 5 nM and 50 nM) can be absorbed by cells and cause severe reactive oxygen species (ROS) production, oxidative stress, and inflammation. Additionally, the expression of NF-κB, caspase-1, and NLRP3 were decreased after pretreatment with ROS scavenging agent N-acetylcysteine (NAC, 5 mM pretreated for 2 h) and the NF-κB nuclear translocation inhibitor Dehydroxymethylepoxyquinomicin (DHMEQ, 10 μg/mL pretreatment for 4 h) respectively. The results indicate that the activation of the NF-κB pathway by ROS not only directly promotes the expression of inflammatory factors such as pro-IL-1β, TNF-α, and IL-6, but also mediates the assembly of NLRP3 by ROS activation of NF-κB pathway, which indirectly promotes the expression of NLRP3. Finally, a high-degree of overlap between the expression of the NF-κB and NLRP3 and the activated regions of KCs, further support the importance of KCs in inflammation induced by low-dose CdTe QDs.
Volume 47
Pages 102157
Published 2021-11-1
DOI 10.1016/j.redox.2021.102157
PII S2213-2317(21)00317-7
PMID 34614473
PMC PMC8489155
MeSH Cadmium Compounds* / toxicity Chemical and Drug Induced Liver Injury* / etiology Humans Inflammasomes NF-kappa B NLR Family, Pyrin Domain-Containing 3 Protein* Quantum Dots* / toxicity Reactive Oxygen Species Tellurium / toxicity
IF 9.986
Human and Animal Cells KUP5(RCB4627)