Cellular consequences triggered by ketamine on exposure to human glioblastoma epithelial (LN-229) cells

J Biochem Mol Toxicol. 2023 Dec;37(12):e23484. doi: 10.1002/jbt.23484. Epub 2023 Jul 29.

Abstract

Ketamine is generally a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that interrelates with various other receptors, contributing to a wide range of actions. They are mainly approved as a general anesthetic, but a low dose of ketamine is applied for pain management, depression, and as analgesics. However, there is a significant concern regarding the long-term usage as antidepressants and as an abused drug. The study mainly aims to exhibit the possible long-term side effects of ketamine as an antidepressant and in recreational users. The study explores the in vitro cytotoxicity revealed on LN-229 cells in a dose-dependent manner. According to the cell viability assays, there is a dose-dependent response toward ketamine. Morphological and nuclear integrity was changed on exposure and assessed using Giemsa, Rhodamine phalloidin, 4',6-diamidino-2-phenylindole (DAPI), and Acridine orange staining. The apoptotic cell death marked by nuclear condensation, Lactate dehydrogenase leakage, pro-inflammatory cytokine (interleukin [IL]-β) release, and inhibition of cell migration was observed. The study highlights the importance of nonanesthetic usage of ketamine, which can lead to severe adverse side effects on long-term exposure rather than a single exposure as an anesthetic agent.

Keywords: anesthetic agent; apoptosis; cell migration; ketamine; nuclear integrity.

MeSH terms

  • Analgesics / adverse effects
  • Apoptosis
  • Glioblastoma*
  • Humans
  • Ketamine* / toxicity
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • Ketamine
  • Receptors, N-Methyl-D-Aspartate
  • Analgesics