Oxidative stress and cytotoxic effects of silver ion in mouse lung macrophages J774.1 cells. Issue 4 (14th September 2016)

• Record Type: Journal Article
• Authors: Shim, Ilseob; Choi, Kyunghee; Hirano, Seishiro
• Is Part Of: Journal of applied toxicology. Volume 37:Issue 4(2017)
• Page Start: 471
• Page End: 478
• Publication Date: 2016-09-14
• Subjects: Silver ion -- Glutathione -- MAP Kinase -- Metallothionein -- Macrophage -- Caspase; Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3382
• Languages: English
• ISSNs: 0260-437X

Abstract

Abstract: Silver is commonly used as a disinfectant, and chronic exposure to silver may cause argyria, resulting in a gray–blue discoloration of human skin. However, the mechanism for cellular toxicity of silver has not been well explained. We studied the mode of cell death, the ratio of glutathione disulfide/glutathione, induction of metallothionein and activation of mitogen‐activated protein kinases in J774.1 cells together with activation of antioxidant responsive element and nuclear factor‐κB in CHO cells following exposure to silver ion (Ag + ) to investigate the mechanism by which Ag + causes lethal effects. Ag + increased phosphorylation levels of extracellular signal‐regulated, c‐Jun N‐terminal and p38 mitogen‐activated protein kinases and remarkably increased the ratio of glutathione disulfide/glutathione in both a time‐ and concentration‐dependent manner. Luciferase reporter gene assays revealed that antioxidant responsive element and nuclear factor‐κB were activated following exposure to Ag + . In addition, exposure to Ag + increased the mRNA and protein levels of metallothionein. We investigated whether or not Ag + killed J774.1 cells by inducing apoptosis. Ag + increased the activity of caspase‐3/7 which was abrogated by caspase 3 and pan‐caspase inhibitors. However, these inhibitors did not ameliorate the cytotoxic effects of Ag +, suggesting that Ag + causes oxidative stress, which leads to necrotic rather than apoptotic cell death in J774.1 cells by decreasing functional sulfhydryl groups including glutathione in the cells. Copyright © 2016 John Wiley & Sons, Ltd. Abstract : Cytotoxic effects of silver ion (Ag + ) were investigated. Ag + caused oxidative stress, activated mitogen‐activated protein kinase, and rapidly and remarkably decreased glutathione level with a reciprocal induction of metallothionein in J774.1 cells. The reporter gene assay indicated that Ag + activated both antioxidant responsive element and nuclear factor‐κB pathways. Ag + also increased the activity of caspase‐3/7. However, caspase inhibitors did not ameliorate the cell viability, suggesting that the mode of cell death was necrotic rather than apoptotic.