Triclosan induces PC12 cells injury is accompanied by inhibition of AKT/mTOR and activation of p38 pathway

• Published in: Neurotoxicology (Park Forest South) Vol. 74; pp. 221 - 229
• Main Authors: Li, Shao-Jun, Chen, Pan, Peres, Tanara Vieira, Villahoz, Beatriz Ferrer, Zhang, Ziyan, Miah, Mahfuzur R., Aschner, Michael
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-09-2019; Elsevier BV
• Subjects: Acetylcysteine; Activation; AKT protein; AKT/mTOR pathway; Animals; Anti-Infective Agents, Local - toxicity; Apoptosis; Apoptosis Regulatory Proteins - biosynthesis; Apoptosis Regulatory Proteins - drug effects; Apoptosis Regulatory Proteins - genetics; Bax protein; Bcl-2 protein; Cell differentiation; Cell Survival - drug effects; Cell viability; Cytotoxicity; Disinfectants; Fungi; Gene expression; L-Lactate Dehydrogenase - metabolism; MAP kinase; Metabolic Networks and Pathways - drug effects; mRNA; Neurotoxicity; Oncogene Protein v-akt - drug effects; Oxidative stress; Oxidative Stress - drug effects; p38; p38 Mitogen-Activated Protein Kinases - drug effects; PC12; PC12 Cells; Pheochromocytoma cells; Phosphorylation; Protein expression; Proteins; Protozoa; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Side effects; TOR protein; TOR Serine-Threonine Kinases - drug effects; Triclosan; Triclosan - toxicity; PC12; Triclosan; AKT/mTOR pathway; p38; Apoptosis
• ISSN: 0161-813X; 1872-9711
• DOI: 10.1016/j.neuro.2019.07.008

•TCS is cytotoxic to PC12 cells causing a decrease in cell viability and inducing cell membrane damages.•TCS increased mRNA and protein expressions of apoptosis-related gene Bax with no alterations in Bcl-2 in PC12 cells.•TCS increased the generation of reactive oxygen species in PC12 cells; pretreatment with N-acetyl cysteine, normalized the effect to control levels.•TCS suppressed the Akt/mTOR pathway in PC12 cells, concomitant with activated the p38 MAPK pathway.
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.