The common anesthetic, sevoflurane, induces apoptosis in A549 lung alveolar epithelial cells

Mol Med Rep. 2014 Jan;9(1):197-203. doi: 10.3892/mmr.2013.1806. Epub 2013 Nov 18.

Abstract

Lung alveolar epithelial cells are the first barrier exposed to volatile anesthetics, such as sevoflurane, prior to reaching the targeted neuronal cells. Previously, the effects of volatile anesthetics on lung surfactant were studied primarily with physicochemical models and there has been little experimental data from cell cultures. Therefore it was investigated whether sevoflurane induces apoptosis of A549 lung epithelial cells. A549 cells were exposed to sevoflurane via a calibrated vaporizer with a 2 l/min flow in a gas‑tight chamber at 37˚C. The concentration of sevoflurane in Dulbecco's modified Eagle's medium was detected with gas chromatography. Untreated cells and cells treated with 2 µM daunorubicin hydrochloride (DRB) were used as negative and positive controls, respectively. Apoptosis factors, including the level of ATP, apoptotic‑bodies by terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling (TUNEL) assay, DNA damage and the level of caspase 3/7 were analyzed. Cells treated with sevoflurane showed a significant reduction in ATP compared with untreated cells. Effects in the DRB group were greater than in the sevoflurane group. The difference of TUNEL staining between the sevoflurane and untreated groups was statistically significant. DNA degradation was observed in the sevoflurane and DRB groups, however this was not observed in the untreated group. The sevoflurane and DRB groups induced increased caspase 3/7 activation compared with untreated cells. These results suggest that sevoflurane induces apoptosis in A549 cells. In conclusion, 5% sevoflurane induced apoptosis of A549 lung alveolar epithelial cells, which resulted in decreased cell viability, increased apoptotic bodies, impaired DNA integrality and increased levels of caspase 3/7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Line, Tumor
  • DNA Damage / drug effects
  • Gases / chemistry
  • Gases / metabolism
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Methyl Ethers / pharmacology*
  • Sevoflurane
  • Temperature

Substances

  • Anesthetics, Inhalation
  • Gases
  • Methyl Ethers
  • Sevoflurane
  • Caspase 3
  • Caspase 7