PMID- 34408413 OWN - NLM STAT- MEDLINE DCOM- 20211004 LR - 20220425 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 16 DP - 2021 TI - Size-Dependent Cytotoxicity and Reactive Oxygen Species of Cerium Oxide Nanoparticles in Human Retinal Pigment Epithelia Cells. PG - 5333-5341 LID - 10.2147/IJN.S305676 [doi] AB - PURPOSE: The use of cerium oxide nanoparticles (CeO(2) NPs), a lanthanide element oxide and bivalent compound, has been growing continuously in industry and biomedicine. Due to their wide application, the potential human health problems of CeO(2) NPs have attracted attention, but studies on the toxicity of this compound to human eyes are lacking. This study investigated the cytotoxicity and reactive oxygen species (ROS) of CeO(2) NPs in human retinal pigment epithelial cells (ARPE-19 cells). METHODS: Using the transmission electron microscope (TEM), the size distribution and shape of CeO(2) NPs were characterized. To explore the effect of CeO(2) NP size on ophthalmic toxicity in vitro, three sizes (15, 30 and 45 nm) of CeO(2) NPs were investigated using ATP content measurement, LDH release measurement and cell proliferation assay in ARPE-19 cells. ROS values and mitochondrial membrane potential depolarization were evaluated by H(2)DCF-DA staining and JC-1 staining. Morphology changes were detected using a phase-contrast microscope. RESULTS: The cytotoxicity of 15 nm CeO(2) NPs was found to be the highest and hence was further explored. Treatment with 15 nm CeO(2) NPs caused the morphology of ARPE-19 cells to change in a dose- and time-dependent manner. Moreover, the treatment induced excessive ROS generation and mitochondrial membrane potential depolarization. In addition, cytotoxicity was attenuated by the application of a ROS scavenger N-acetyl-L- cysteine (NAC). CONCLUSION: CeO(2) NPs induced cytotoxicity in ARPE-19 cells and excessive production of ROS and decreasing mitochondrial membrane potential. The Overproduction of ROS partially contributes to CeO(2) NP-induced cytotoxicity. CI - (c) 2021 Ma et al. FAU - Ma, Yuanyuan AU - Ma Y AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Li, Peng AU - Li P AD - Department of Nephrology Yantai Yuhuangding Hospital, Qingdao University, Yantai, 264005, Shandong, People's Republic of China. FAU - Zhao, Laien AU - Zhao L AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Liu, Jia AU - Liu J AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Yu, Jinguo AU - Yu J AD - Department of Ophthalmology, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China. FAU - Huang, Yanmei AU - Huang Y AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Zhu, Yuting AU - Zhu Y AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Li, Zelin AU - Li Z AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Zhao, Ruikang AU - Zhao R AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Hua, Shaofeng AU - Hua S AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Zhu, Yanping AU - Zhu Y AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. FAU - Zhang, Zhuhong AU - Zhang Z AD - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, People's Republic of China. LA - eng PT - Journal Article DEP - 20210810 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Reactive Oxygen Species) RN - 0 (Retinal Pigments) RN - 30K4522N6T (Cerium) RN - 619G5K328Y (ceric oxide) SB - IM MH - Cerium/toxicity MH - Humans MH - *Metal Nanoparticles/toxicity MH - Reactive Oxygen Species MH - Retinal Pigments PMC - PMC8364434 OTO - NOTNLM OT - mitochondrial membrane potential depolarization OT - nanomaterials OT - ophthalmic toxicity OT - oxidative stress COIS- The authors report no conflicts of interest in this work. EDAT- 2021/08/20 06:00 MHDA- 2021/10/05 06:00 PMCR- 2021/08/10 CRDT- 2021/08/19 06:36 PHST- 2021/02/06 00:00 [received] PHST- 2021/07/07 00:00 [accepted] PHST- 2021/08/19 06:36 [entrez] PHST- 2021/08/20 06:00 [pubmed] PHST- 2021/10/05 06:00 [medline] PHST- 2021/08/10 00:00 [pmc-release] AID - 305676 [pii] AID - 10.2147/IJN.S305676 [doi] PST - epublish SO - Int J Nanomedicine. 2021 Aug 10;16:5333-5341. doi: 10.2147/IJN.S305676. eCollection 2021.