PMID- 23416263 OWN - NLM STAT- MEDLINE DCOM- 20130918 LR - 20220318 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 27 IP - 3 DP - 2013 Apr TI - Cerium oxide nanoparticles induce cytotoxicity in human hepatoma SMMC-7721 cells via oxidative stress and the activation of MAPK signaling pathways. PG - 1082-8 LID - S0887-2333(13)00028-3 [pii] LID - 10.1016/j.tiv.2013.02.005 [doi] AB - BACKGROUND: Lanthanide cerium oxide (CeO2) nanoparticles have extensive applications in industrial fields, and concerns regarding their potential toxicity in humans and their environmental impact have increased. We investigated the underlying molecular mechanisms by which CeO2 nanoparticles induce toxicity in human hepatoma SMMC-7721 cells. RESULTS: Our results demonstrated that CeO2 nanoparticles reduced viability, caused dramatic morphological damage, and induced apoptosis in SMMC-7721 cells. CeO2 nanoparticles significantly increased the production of reactive oxygen species (ROS) and malondialdehyde (MDA), and significantly reduced the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-px) and catalase (CAT). The phosphorylation levels of ERK1/2, JNK and p38 MAPK were significantly elevated after treatment with CeO2 nanoparticles. Pretreatment with the antioxidant N-acetyl-cysteine (NAC): reduced the induction of ROS and MDA by CeO2 nanoparticles; recovered the activity of SOD, GSH-px and CAT; reduced the phosphorylation levels of ERK1/2, JNK and p38; and attenuated CeO2 nanoparticles-induced damage and apoptosis in SMMC-7721 cells. CONCLUSIONS: Our data demonstrated that CeO2 nanoparticles induced damage and apoptosis in human SMMC-7721 cells via oxidative stress and the activation of MAPK signaling pathways. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Cheng, Guilin AU - Cheng G AD - Institute of Chemicals Safety, Chinese Academy of Inspection and Quarantine, PR China. FAU - Guo, Wei AU - Guo W FAU - Han, Lu AU - Han L FAU - Chen, Erlei AU - Chen E FAU - Kong, Lingfang AU - Kong L FAU - Wang, Lili AU - Wang L FAU - Ai, Wenchao AU - Ai W FAU - Song, Naining AU - Song N FAU - Li, Haishan AU - Li H FAU - Chen, Huiming AU - Chen H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130214 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Antioxidants) RN - 0 (Reactive Oxygen Species) RN - 30K4522N6T (Cerium) RN - 4Y8F71G49Q (Malondialdehyde) RN - 619G5K328Y (ceric oxide) RN - EC 1.11.1.6 (Catalase) RN - EC 1.11.1.9 (Glutathione Peroxidase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - Antioxidants/pharmacology MH - Apoptosis/drug effects MH - Carcinoma, Hepatocellular MH - Catalase/metabolism MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Cerium/*toxicity MH - Glutathione Peroxidase/metabolism MH - Humans MH - MAP Kinase Signaling System/drug effects MH - Malondialdehyde/metabolism MH - Mitogen-Activated Protein Kinases/metabolism MH - Nanoparticles/*toxicity MH - Oxidative Stress/drug effects MH - Reactive Oxygen Species/metabolism MH - Superoxide Dismutase/metabolism EDAT- 2013/02/19 06:00 MHDA- 2013/09/21 06:00 CRDT- 2013/02/19 06:00 PHST- 2012/09/10 00:00 [received] PHST- 2013/01/05 00:00 [revised] PHST- 2013/02/05 00:00 [accepted] PHST- 2013/02/19 06:00 [entrez] PHST- 2013/02/19 06:00 [pubmed] PHST- 2013/09/21 06:00 [medline] AID - S0887-2333(13)00028-3 [pii] AID - 10.1016/j.tiv.2013.02.005 [doi] PST - ppublish SO - Toxicol In Vitro. 2013 Apr;27(3):1082-8. doi: 10.1016/j.tiv.2013.02.005. Epub 2013 Feb 14.