An In Vitro Study of the Neurotoxic Effects of N-Benzylpiperazine: A Designer Drug of Abuse

Neurotox Res. 2016 May;29(4):558-68. doi: 10.1007/s12640-016-9604-x. Epub 2016 Feb 9.

Abstract

Recently, the number of new psychoactive substances has significantly increased. Despite the systematic introduction of prohibition in trade of medicinal products which mimic the effects of illegal drugs, the problem concerning this group of drugs is still important although knowledge about the mechanism of action of those types of substances is scarce. This study aimed to follow the neurotoxic effect of N-benzylpiperazine (BZP), the central nervous system psychostimulant, using the human cancer LN-18 cell model. The statistically significant elevation of LDH levels, increased mitochondrial membrane potential, decreased ATP and increased ROS production, increased levels of DNA damage marker (8-OHdG) and activation of caspases: -3 and -9 confirmed by Real-Time PCR imply the activation of mitochondrial proapoptotic pathways induced by BZP after 24 h incubation. This study is a novel, preliminary attempt to explain the toxicity of one of the most popular designer drug of abuse at the cellular level.

Keywords: Apoptosis; Benzylpiperazine; Neurodegeneration; New psychoactive substances; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adenosine Triphosphate / metabolism
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Line, Tumor
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma / pathology
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Membrane Potential, Mitochondrial / drug effects*
  • Neurotoxins / pharmacology*
  • Piperazines / pharmacology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • N-benzylpiperazine
  • Neurotoxins
  • Piperazines
  • Proto-Oncogene Proteins c-bcl-2
  • RELA protein, human
  • RNA, Messenger
  • Reactive Oxygen Species
  • Transcription Factor RelA
  • bcl-2-Associated X Protein
  • 8-Hydroxy-2'-Deoxyguanosine
  • Adenosine Triphosphate
  • L-Lactate Dehydrogenase
  • Caspases
  • Deoxyguanosine