Title: Triclosan induces PC12 cells injury is accompanied by inhibition of AKT/mTOR and activation of p38 pathway.
Authors: Li, Shao-Jun; Chen, Pan; Peres, Tanara Vieira; Villahoz, Beatriz Ferrer; Zhang, Ziyan; Miah, Mahfuzur R; Aschner, Michael
Published In Neurotoxicology, (2019 09)
Abstract: Triclosan (TCS) has been widely used as a disinfectant and antiseptic in multiple consumer and healthcare products due to its clinical effectiveness against various bacteria, fungi and protozoa. Recently, several studies have reported the adverse effects of TCS on various nerve cells, arousing concerns about its potential neurotoxicity. The present study aimed to investigate the neurotoxicity of TCS in rat pheochromocytoma PC12 cells. After differentiation, the stabilized PC12 cells were treated with 1, 10, 50 μM TCS for 12 h. At the end of the treatment, the generation of reactive oxygen species (ROS), protein expression of apoptotic-related genes, AMPK-AKT/mTOR, as well as p38 in PC12 cells were determined. The concentrations were chosen based on the results of cell viability and lactic dehydrogenase (LDH) assays in response to TCS treatment (ranging from 0.001 to 100 μM) for varied time periods. The results showed that TCS is cytotoxic to PC12 cells, causing decreased cell viability accompanied by increased LDH release. TCS treatment at 10 and 50 μM for 12 h increased the mRNA and protein expression of the pro-apoptotic gene Bax, while Bcl-2 levels remained unchanged. Moreover, an increase in the generation of reactive oxygen species (ROS) was found in TCS-treated PC12 cells at the concentrations of 1 and 10 μM. Pretreatment with 100 μM N-acetyl cysteine (NAC- ROS scavenger) for 1 h normalized the ROS generations in TCS-treated PC12 cells. Additionally, the suppression of the phosphorylation of Akt and mTOR was observed in TCS-treated PC12 cells at 10 and 50 μM for 12 h, concomitant with the activation of p38 MAPK pathway at 50 μM TCS. However, there were no effects of TCS on the phosphorylation of AMPK in these cells. Taken together, these results suggest that TCS may cause adverse effects and oxidative stress in PC12 cells accompanied by inhibition of Akt/mTOR and activation of p38.
PubMed ID: 31381933
MeSH Terms: Animals; Anti-Infective Agents, Local/toxicity*; Apoptosis Regulatory Proteins/biosynthesis; Apoptosis Regulatory Proteins/drug effects; Apoptosis Regulatory Proteins/genetics; Cell Survival/drug effects; L-Lactate Dehydrogenase/metabolism; Metabolic Networks and Pathways/drug effects*; Oncogene Protein v-akt/drug effects*; Oxidative Stress/drug effects; PC12 Cells; Phosphorylation; Rats; Reactive Oxygen Species/metabolism; TOR Serine-Threonine Kinases/drug effects*; Triclosan/toxicity*; p38 Mitogen-Activated Protein Kinases/drug effects*