Open AccessN ‐acetylcysteine Attenuates Cobalt Nanoparticle‐Induced Cytotoxic Effects through Inhibition of Cell Death, Reactive Oxygen Species‐related Signaling and Cytokines Expression
Author(s) -
Liu Yake,
Yang Hongwei,
Wang Menghong,
Wang Wei,
Liu Fan,
Yang Huilin
Publication year - 2016
Publication title -
orthopaedic surgery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 23
eISSN - 1757-7861
pISSN - 1757-7853
DOI - 10.1111/os.12298
Subject(s) - reactive oxygen species , p38 mitogen activated protein kinases , viability assay , apoptosis , mapk/erk pathway , microbiology and biotechnology , annexin , chemistry , cytotoxicity , oxidative stress , signal transduction , biochemistry , biology , in vitro
Objective Complex cobalt‐chromium alloys, bearing surfaces of the second‐generation metal‐on‐metal ( M o M ) hip prostheses, are subject to wear and generate cobalt nanoparticles ( C o NP s). C o NP s could reduce cellular viability, activate the mitogen‐activated protein kinase ( MAPK ) pathway and increase cell apoptosis via reactive oxygen species ( ROS ). However, the detailed mechanisms of ROS functioning on C o NP ‐mediated signaling molecules and cytotoxicity has not yet been fully demonstrated. The present study investigated the functional role of N ‐acetylcysteine ( NAC ) in reversing the activation of ROS signaling pathways triggered by C o NP s in normal mice kidney cells ( TCMK ‐1 cells). Methods After being pretreated with NAC , TCMK ‐1 cells were treated with 300–700 μmol/ L C o NP s, then, CCK ‐8 assay was used to verify the survival of TCMK ‐1 cells. Annexin V/PI staining was performed to investigate the apoptosis of TCMK ‐1 cells after NAC and different concentrations of C o NP treatments. In addition, western blot was performed to identify the cytokine (p‐ ERK , p‐p38, and p‐ JNK ) expression of the ROS ‐related MAPK signaling pathway. Results Apoptosis rate of TCMK ‐1 cells was increased obviously after different concentrations of C o NP treatment. However, TCMK ‐1 cells, pretreated with NAC , exhibited a significantly decreased apoptosis rate. In addition, p‐ ERK , p‐p38, and p‐ JNK expressions were increased with C o NP treatment, which indicated that C o NP s could activate the MAPK pathway. Interestingly, this entire stimulated phenomenon by C o NP s was reversed with NAC treatment. Conclusions These findings indicated that NAC could reverse C o NP ‐induced cytotoxicity by inhibiting ROS ‐induced cell death and cytokine expression. To our knowledge, this is the first report that describes how C o NP ‐induced cytotoxicity in TCMK ‐1 cells could be attenuated by anti‐oxidative agents ( NAC) , which may function through inhibition of cell death and ROS .