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Exposure of isoflurane-treated cells to hyperoxia decreases cell viability and activates the mitochondrial apoptotic pathway.
- Source :
-
Brain research [Brain Res] 2016 Apr 01; Vol. 1636, pp. 13-20. Date of Electronic Publication: 2016 Feb 05. - Publication Year :
- 2016
-
Abstract
- Isoflurane has either neuroprotective or neurotoxic effects. High-dose oxygen is frequently used throughout the perioperative period. We hypothesized that hyperoxia will affect cell viability of rat pheochromocytoma (PC12) cells that were exposed to isoflurane and reactive oxygen species (ROS) may be involved. PC12 cells were exposed to 1.2% or 2.4% isoflurane for 6 or 24h respectively, and cell viability was evaluated. To investigate the effects of hyperoxia, PC12 cells were treated with 21%, 50%, or 95% oxygen and 2.4% isoflurane for 6h, and cell viability, TUNEL staining, ROS production, and expression of B-cell lymphoma 2 (BCL-2), BCL2-associated X protein (BAX), caspase-3 and beta-site APP cleaving enzyme (BACE) were measured. ROS involvement was evaluated using the ROS scavenger 2-mercaptopropiopylglycine (MPG). The viability of cells exposed to 2.4% isoflurane was lower than that of cells exposed to 1.2% isoflurane. Prolonged exposure (6h vs. 24h) to 2.4% isoflurane resulted in a profound reduction in cell viability. Treatment with 95% (but not 50%) oxygen enhanced the decrease in cell viability induced by 2.4% isoflurane alone. Levels of ROS, Bax, caspase-3 and BACE were increased, whereas expression of Bcl-2 was decreased, in cells treated with 95% oxygen plus 2.4% isoflurane compared with the control and 2.4% isoflurane plus air groups. MPG attenuated the effects of oxygen and isoflurane. In conclusion, isoflurane affects cell viability in a dose- and time-dependent manner. This effect is augmented by hyperoxia and may involve ROS, the mitochondrial apoptotic signaling pathway, and β-amyloid protein.<br /> (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Cell Survival drug effects
In Situ Nick-End Labeling
PC12 Cells
Proto-Oncogene Proteins c-bcl-2 metabolism
Rats
Reactive Oxygen Species metabolism
Statistics, Nonparametric
Time Factors
bcl-2-Associated X Protein metabolism
Anesthetics, Inhalation pharmacology
Apoptosis drug effects
Hyperoxia metabolism
Isoflurane pharmacology
Mitochondria drug effects
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1872-6240
- Volume :
- 1636
- Database :
- MEDLINE
- Journal :
- Brain research
- Publication Type :
- Academic Journal
- Accession number :
- 26854136
- Full Text :
- https://doi.org/10.1016/j.brainres.2016.01.052