期刊
REDOX BIOLOGY
卷 47, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.redox.2021.102157
关键词
Cd telluride quantum dots; Low-dose exposure; Reactive oxygen species; Hepatic macrophages (Kupffer cell); NLRP3 inflammasome
资金
- National Natural Science Foundation of China [81673218]
- Natural Science Foundation of Jiangsu Province [BK20201268]
This study found that low-dose exposure to CdTe QDs can activate hepatic macrophages, causing inflammation and oxidative stress. The activation of the NF-kappa B and NLRP3 pathways plays a crucial role in this process.
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 mu M/kg center dot bw and 10 mu M/kg center dot 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-kappa B, caspase-1, and NLRP3 were decreased after pretreatment with ROS scavenging agent N-acetylcysteine (NAC, 5 mM pretreated for 2 h) and the NF-kappa B nuclear translocation inhibitor Dehydroxymethylepoxyquinomicin (DHMEQ, 10 mu g/mL pretreatment for 4 h) respec-tively. The results indicate that the activation of the NF-kappa B pathway by ROS not only directly promotes the expression of inflammatory factors such as pro-IL-113, TNF-alpha, and IL-6, but also mediates the assembly of NLRP3 by ROS activation of NF-kappa B pathway, which indirectly promotes the expression of NLRP3. Finally, a high-degree of overlap between the expression of the NF-kappa B and NLRP3 and the activated regions of KCs, further support the importance of KCs in inflammation induced by low-dose CdTe QDs.
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