title: Exposure of isoflurane-treated cells to hyperoxia decreases cell viability and activates the mitochondrial apoptotic pathway.
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.
authors: Department of Anesthesiology and Pain Medicine, National Medical Center, South Korea.
authors: Gunn Hee
authors: GH
authors: Kim
authors: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea. Electronic address: ljj6625@gmail.com.
authors: Jeong Jin
authors: JJ
authors: Lee
authors: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea.
authors: Sang Hyun
authors: SH
authors: Lee
authors: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea.
authors: Yang Hoon
authors: YH
authors: Chung
authors: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea.
authors: Hyun Sung
authors: HS
authors: Cho
authors: Department of Anesthesiology and Pain Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-gu, Seoul 135-710, South Korea.
authors: Jie Ae
authors: JA
authors: Kim
authors: Samsung Biomedical Research Institute, Seoul, South Korea.
authors: Min Kyung
authors: MK
authors: Kim
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018496:Hyperoxia / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D007530:Isoflurane / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018709:Statistics, Nonparametric; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D007530:Isoflurane
keywords: Alzheimer׳s disease