Pregabalin reduces oxaliplatin-induced oxidative neurotoxicity through modulation of TRPV1 channels in DBTRG neuronal cell line

Anticancer Drugs. 2020 Aug;31(7):728-736. doi: 10.1097/CAD.0000000000000949.


As a member of the platinum drug group, oxaliplatin (OXAL) is used to treat brain tumors, although its use is limited through excessive calcium ion (Ca) influx and reactive oxygen species (ROS) production in neurons. The Ca permeable transient receptor potential vanilloid 1 (TRPV1) channel is activated by ROS, and its activity might be reduced by the antioxidant property of pregabalin (PREGAB). This study aimed to investigate the protective action of PREGAB against OXAL-induced oxidative neurotoxicity in human glioblastoma (DBTRG) cells. The DBTRG cells were divided into four treatment groups: control, PREGAB (500 µM for 1 h), OXAL (25 µM for 24 h), and PREGAB + OXAL. In the laser confocal microscope and plate reader analyses, apoptosis, mitochondrial membrane depolarization (JC-1), cell death (propidium iodide/Hoechst rate), and ROS-level production increased by activating TRPV1 in the cells using the OXAL treatment, although the cell viability values decreased. However, these values were recovered in the PREGAB + OXAL group using PREGAB and TRPV1 inhibitor (capsazepine) treatments. In the patch-clamp analyses, OXAL-induced TRPV1 channel activation in the OXAL group also decreased in the PREGAB + OXAL group using the PREGAB and capsazepine treatments. In conclusion, the apoptosis and oxidant actions of OXAL were increased by activation of the TRPV1 channel, but this effect was diminished by the PREGAB treatment. PREGAB treatment has the potential to be an effective strategy in the treatment of OXAL-induced oxidative neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Calcium / metabolism
  • Caspase 3 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Drug Interactions
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / prevention & control*
  • Oxaliplatin / adverse effects
  • Oxaliplatin / pharmacology*
  • Oxidative Stress / drug effects
  • Patch-Clamp Techniques
  • Pregabalin / pharmacology*
  • Reactive Oxygen Species / metabolism
  • TRPV Cation Channels / antagonists & inhibitors
  • TRPV Cation Channels / metabolism*


  • Reactive Oxygen Species
  • TRPV Cation Channels
  • TRPV1 protein, human
  • Oxaliplatin
  • Pregabalin
  • CASP3 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 9
  • Calcium