title: Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis.
abstract: Silver nanoparticles (AgNPs), which have well-known antimicrobial properties, are extensively used in various medical and general applications. Despite the widespread use of AgNPs, relatively few studies have been undertaken to determine the cytotoxic effects of AgNPs exposure. This study investigates possible molecular mechanisms underlying the cytotoxic effects of AgNPs. Here, we show that AgNPs-induced cytotoxicity was higher compared than that observed when AgNO(3) was used as a silver ion source. AgNPs induced reactive oxygen species (ROS) generation and suppression of reduced glutathione (GSH) in human Chang liver cells. ROS generated by AgNPs resulted in damage to various cellular components, DNA breaks, lipid membrane peroxidation, and protein carbonylation. Upon AgNPs exposure, cell viability decreased due to apoptosis, as demonstrated by the formation of apoptotic bodies, sub-G(1) hypodiploid cells, and DNA fragmentation. AgNPs induced a mitochondria-dependent apoptotic pathway via modulation of Bax and Bcl-2 expressions, resulting in the disruption of mitochondrial membrane potential (Δψ(m)). Loss of Δψ(m) was followed by cytochrome c release from the mitochondria, resulting in the activation of caspases 9 and 3. The apoptotic effect of AgNPs was exerted via the activation of c-Jun NH(2)-terminal kinase (JNK) and was abrogated by the JNK-specific inhibitor, SP600125 and siRNA targeting JNK. In summary, the results suggest that AgNPs cause cytotoxicity by oxidative stress-induced apoptosis and damage to cellular components.
authors.affiliation: School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju 690-756, Republic of Korea.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.forename: Kyoung Ah
authors.initials: KA
authors.lastname: Kang
authors.forename: In Kyung
authors.initials: IK
authors.lastname: Lee
authors.forename: Hye Sun
authors.initials: HS
authors.lastname: Kim
authors.forename: Suhkmann
authors.initials: S
authors.lastname: Kim
authors.forename: Jeong Yun
authors.initials: JY
authors.lastname: Choi
authors.forename: Jinhee
authors.initials: J
authors.lastname: Choi
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D008928:Mitochondria / Q000502:physiology*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D012834:Silver / Q000633:toxicity*
chemical_list: D017382:Reactive Oxygen Species; D012834:Silver; D020169:Caspases; D005978:Glutathione