N-Acetyl Cysteine (NAC)-Directed Detoxification of Methacryloxylethyl Cetyl Ammonium Chloride (DMAE-CB)

PLoS One. 2015 Aug 14;10(8):e0135815. doi: 10.1371/journal.pone.0135815. eCollection 2015.

Abstract

Methacryloxylethyl cetyl ammonium chloride (DMAE-CB) is a polymerizable antibacterial monomer and has been proved as an effective strategy to achieve bioactive bonding with reliable bacterial inhibitory effects. However, the toxicity of DMAE-CB may hamper its wide application in clinical situations. Thus, this study was designed to investigate the toxicity of DMAE-CB and explore the possible protective effects of N-acetyl cysteine (NAC). High performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analysis showed that chemical binding of NAC and DMAE-CB occurred in a time dependent manner. Pre-incubation of fourty-eight hours is required for adequate reaction between DMAE-CB and NAC. DMAE-CB reduced human dental pulp cells (hDPCs) viability in a dose-dependent manner. The toxic effects of DMAE-CB were accompanied by increased reactive oxygen species (ROS) level and reduced glutathione (GSH) content. NAC alleviated DMAE-CB-induced oxidative stress. Annexin V/ Propidium Iodide (PI) staining and Hoechst 33342 staining indicated that DMAE-CB induced apoptosis. Collapsed mitochondrial membrane potential (MMP) and activation of caspase-3 were also observed after DMAE-CB treatment. NAC rescued hDPCs from DMAE-CB-induced apoptosis, accompanied by lower level of MMP loss and caspase-3 activity. This study assists to elucidate the mechanism underlying the cytotoxic effects of DMAE-CB and provides theoretical supports for the searching of effective strategies to reduce toxicity of quaternary ammonium dental monomers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Adolescent
  • Adult
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Dental Pulp / metabolism*
  • Dental Pulp / pathology
  • Female
  • Humans
  • Male
  • Mass Spectrometry
  • Methacrylates / toxicity*
  • Oxidative Stress / drug effects*
  • Quaternary Ammonium Compounds / toxicity*

Substances

  • Methacrylates
  • Quaternary Ammonium Compounds
  • methacryloxylethyl cetyl dimethyl ammonium
  • CASP3 protein, human
  • Caspase 3
  • Acetylcysteine

Grants and funding

This study was financially supported by grant 81130078 (principal investigator JC) and grant 81300927 (principal investigator SM) from the National Nature Science Foundation of China, and Program No. IRT13051 from the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.