title: Toxicological Effects of Caco-2 Cells Following Short-Term and Long-Term Exposure to Ag Nanoparticles.
abstract: Extensive utilization increases the exposure of humans to Ag nanoparticles (NPs) via the oral pathway. To comprehensively address the action of Ag NPs to the gastrointestinal systems in real situations, i.e., the long-term low-dose exposure, we evaluated and compared the toxicity of three Ag NPs (20-30 nm with different surface coatings) to the human intestine cell Caco-2 after 1-day and 21-day exposures, using various biological assays. In both the short- and long-term exposures, the variety of surface coating predominated the toxicity of Ag NPs in a descending order of citrate-coated Ag NP (Ag-CIT), bare Ag NP (Ag-B), and poly (N-vinyl-2-pyrrolidone)-coated Ag NP (Ag-PVP). The short-term exposure induced cell growth inhibition and death. The cell viability loss appeared after cells were exposed to 0.7 μg/mL Ag-CIT, 0.9 μg/mL Ag-B or >1.0 μg/mL Ag-PVP for 24 h. The short-term and higher-dose exposure also induced reactive oxygen species (ROS) generation, mitochondrial damage, cell membrane leakage, apoptosis, and inflammation (IL-8 level). The long-term exposure only inhibited the cell proliferation. After 21-day exposure to 0.4 μg/mL Ag-CIT, the cell viability dropped to less than 50%, while cells exposed to 0.5 μg/mL Ag-PVP remained normal as the control. Generally, 0.3 μg/mL is the non-toxic dose for the long-term exposure of Caco-2 cells to Ag NPs in this study. However, cells presented inflammation after exposure to Ag NPs with the non-toxic dose in the long-term exposure.
authors.affiliation: Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China. chenni2686@163.com.
authors.forename: Ni
authors.initials: N
authors.lastname: Chen
authors.affiliation: Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China. szmeismile@126.com.
authors.forename: Zheng-Mei
authors.initials: ZM
authors.lastname: Song
authors.affiliation: Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. huantang@pku.edu.cn.
authors.forename: Huan
authors.initials: H
authors.lastname: Tang
authors.affiliation: Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China. xwsgsy@126.com.
authors.forename: Wen-Song
authors.initials: WS
authors.lastname: Xi
authors.affiliation: Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China. ancao@shu.edu.cn.
authors.forename: Aoneng
authors.initials: A
authors.lastname: Cao
authors.affiliation: Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China. yliu@pku.edu.cn.|Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. yliu@pku.edu.cn.
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Nanochemistry and Nanobiology, Shanghai University, Shanghai 200444, China. hwang@shu.edu.cn.
authors.forename: Haifang
authors.initials: H
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D018938:Caco-2 Cells; D002951:Citrates / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000009:adverse effects* / Q000737:chemistry / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011145:Polyvinyls / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000737:chemistry
chemical_list: D002951:Citrates; D011145:Polyvinyls; D011760:Pyrrolidinones; D017382:Reactive Oxygen Species; D012834:Silver
keywords: Ag nanoparticle; Caco-2 cells; long-term; low-dose; surface coating; toxicity