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Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis.
Toxicol Lett. 2011 Feb 25; 201(1):92-100.TL

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+Show Affiliations

School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju 690-756, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21182908

Citation

Piao, Mei Jing, et al. "Silver Nanoparticles Induce Oxidative Cell Damage in Human Liver Cells Through Inhibition of Reduced Glutathione and Induction of Mitochondria-involved Apoptosis." Toxicology Letters, vol. 201, no. 1, 2011, pp. 92-100.
Piao MJ, Kang KA, Lee IK, et al. Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. Toxicol Lett. 2011;201(1):92-100.
Piao, M. J., Kang, K. A., Lee, I. K., Kim, H. S., Kim, S., Choi, J. Y., Choi, J., & Hyun, J. W. (2011). Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. Toxicology Letters, 201(1), 92-100. https://doi.org/10.1016/j.toxlet.2010.12.010
Piao MJ, et al. Silver Nanoparticles Induce Oxidative Cell Damage in Human Liver Cells Through Inhibition of Reduced Glutathione and Induction of Mitochondria-involved Apoptosis. Toxicol Lett. 2011 Feb 25;201(1):92-100. PubMed PMID: 21182908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Silver nanoparticles induce oxidative cell damage in human liver cells through inhibition of reduced glutathione and induction of mitochondria-involved apoptosis. AU - Piao,Mei Jing, AU - Kang,Kyoung Ah, AU - Lee,In Kyung, AU - Kim,Hye Sun, AU - Kim,Suhkmann, AU - Choi,Jeong Yun, AU - Choi,Jinhee, AU - Hyun,Jin Won, Y1 - 2010/12/21/ PY - 2010/10/15/received PY - 2010/12/06/revised PY - 2010/12/10/accepted PY - 2010/12/25/entrez PY - 2010/12/25/pubmed PY - 2011/3/31/medline SP - 92 EP - 100 JF - Toxicology letters JO - Toxicol Lett VL - 201 IS - 1 N2 - 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. SN - 1879-3169 UR - https://www.unboundmedicine.com/medline/citation/21182908/Silver_nanoparticles_induce_oxidative_cell_damage_in_human_liver_cells_through_inhibition_of_reduced_glutathione_and_induction_of_mitochondria_involved_apoptosis_ DB - PRIME DP - Unbound Medicine ER -