PMID- 36634885 OWN - NLM STAT- MEDLINE DCOM- 20230309 LR - 20230309 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 88 DP - 2023 Apr TI - N-acetyl-L-cysteine attenuated the toxicity of ZIF-8 on EA.hy926 endothelial cells by wnt/beta-catenin pathway. PG - 105553 LID - S0887-2333(23)00002-4 [pii] LID - 10.1016/j.tiv.2023.105553 [doi] AB - As kinds of porous crystalline compounds, zeolitic imidazolate frameworks (ZIFs) have been developed quickly and attracted considerable attention for use in nano drug delivery systems, which raised concerns about cardiovascular disorders. At the present, the cytotoxic mechanism of ZIFs in cardiovascular disorders was still unclear. Our experiment explored the toxicity of ZIF-8, a typical kind of ZIFs, on human EA.hy926 vascular endothelial cells. The cell viability, ROS formation, apoptosis level, inflammatory response level, wound healing ability and atherosclerosis-related indicators of EA.hy926 endothelial cells were analyzed after ZIF-8 treatment. Meanwhile, we evaluated the ability of antioxidant N-Acetyl-L-cysteine (NAC) to attenuate the toxicity of ZIF-8 on EA.hy926 endothelial cells. As results, NAC attenuated ROS formation, cell apoptosis, LDH formation and endothelial dysfunction caused by ZIF-8. As the Wnt/beta-catenin pathway was involved in endothelial cell dysfunction, we also studied the expression level of beta-catenin and LEF1 in ZIF-8 and/or NAC treated EA.hy926 cells. As expected, ZIF-8 increased the protein expressions of beta-catenin and LEF1in the IC50 group, which was significantly inhibited by co-treatment with NAC. Taken together, this study could help improve our understanding about the mechanism of ZIF-8-induced endothelial cells injury and NAC had therapeutic potential in preventing ZIF-8-associated endothelial dysfunction by wnt/beta-catenin pathway. CI - Copyright (c) 2023. Published by Elsevier Ltd. FAU - Tang, Yaxin AU - Tang Y AD - School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. FAU - Jin, Lifang AU - Jin L AD - School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China; Shaoxing Academy of Biomedicine of Zhejiang Sci-Tech University, Shaoxing, Zhejiang, China. FAU - Qi, Wenwen AU - Qi W AD - Xiangzhou District People's Hospital, Xiangyang, Hubei, China. FAU - Gao, Yue AU - Gao Y AD - School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. FAU - Xie, Yixia AU - Xie Y AD - School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. FAU - Xie, Xueying AU - Xie X AD - School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. FAU - Lv, Jianan AU - Lv J AD - School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. FAU - Jiang, Zhikai AU - Jiang Z AD - The Second Clinical Medical College of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Jiang, He AU - Jiang H AD - The First Clinical Medical School of Zhejiang Chinese Medical University, Hangzhou, China. FAU - Fan, Caixia AU - Fan C AD - School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. Electronic address: cxfan2014@sinano.ac.cn. FAU - Yan, Junyan AU - Yan J AD - School of Life Science, Shaoxing University, Shaoxing, Zhejiang, China. Electronic address: jyyan2018@usx.edu.cn. LA - eng PT - Journal Article DEP - 20230110 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - WYQ7N0BPYC (Acetylcysteine) RN - 0 (beta Catenin) RN - 0 (Reactive Oxygen Species) RN - 0 (acidified zeolitic imidazolate framework-8) SB - IM MH - Humans MH - *Acetylcysteine/pharmacology MH - *beta Catenin/metabolism MH - *Endothelial Cells/drug effects/metabolism MH - Reactive Oxygen Species/metabolism MH - Wnt Signaling Pathway OTO - NOTNLM OT - EA.hy926 endothelial cells OT - N-acetyl-L-cysteine (NAC) OT - Toxicity OT - ZIF-8 COIS- Declaration of Competing Interest The authors have no conflicts of interest to declare. EDAT- 2023/01/13 06:00 MHDA- 2023/02/25 06:00 CRDT- 2023/01/12 19:22 PHST- 2022/09/13 00:00 [received] PHST- 2023/01/07 00:00 [revised] PHST- 2023/01/07 00:00 [accepted] PHST- 2023/01/13 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] PHST- 2023/01/12 19:22 [entrez] AID - S0887-2333(23)00002-4 [pii] AID - 10.1016/j.tiv.2023.105553 [doi] PST - ppublish SO - Toxicol In Vitro. 2023 Apr;88:105553. doi: 10.1016/j.tiv.2023.105553. Epub 2023 Jan 10.