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Fraxetin suppresses reactive oxygen speciesādependent autophagy by the PI3K/Akt pathway to inhibit isofluraneāinduced neurotoxicity in hippocampal neuronal cells
- Source :
- Journal of Applied Toxicology. 42:617-628
- Publication Year :
- 2021
- Publisher :
- Wiley, 2021.
-
Abstract
- Isoflurane, a common volatile anesthetic, has been widely used to provide general anesthesia in operations. However, exposure to isoflurane may cause widespread neurotoxicity in the developing animal brain. Fraxetin, a natural coumarin derivative extracted from the bark of Fraxinus rhynchophylla, possesses versatile pharmacological properties including anti-oxidative, anti-inflammatory, and neuroprotective effects. However, the effect and action mechanism of fraxetin on neurotoxicity induced by isoflurane are unknown. Reactive oxygen species (ROS) generation, cell viability, lactate dehydrogenase (LDH) release, and apoptosis were estimated by 2',7'-dichlorofluorescin-diacetate (DCFH-DA) staining, MTT, LDH release, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) staining assays, respectively. The protein levels of light chain 3 (LC3)-I, LC3-II, p62, protein kinase B (Akt), and phosphorylated Akt (p-Akt) were detected by western blot analysis. Isoflurane induced ROS, LDH release, apoptosis, and autophagy, but inhibited the viability in HT22 cells, which were overturned by fraxetin or ROS scavenger N-acetyl-L-cysteine. Fraxetin suppressed isoflurane-induced PI3K/Akt inactivation in HT22 cells. PI3K/Akt inactivation by LY294002 resisted the effects of fraxetin on isoflurane-induced autophagy and autophagy-modulated neurotoxicity in HT22 cells. In conclusion, fraxetin suppressed ROS-dependent autophagy by activating the PI3K/Akt pathway to inhibit isoflurane-induced neurotoxicity in hippocampal neuronal cells.
- Subjects :
- chemistry.chemical_classification
Reactive oxygen species
TUNEL assay
Isoflurane
Chemistry
Autophagy
Neurotoxicity
Apoptosis
Pharmacology
Toxicology
medicine.disease
Hippocampus
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Coumarins
medicine
Animals
Neurotoxicity Syndromes
Fraxetin
Viability assay
Reactive Oxygen Species
Proto-Oncogene Proteins c-akt
Protein kinase B
PI3K/AKT/mTOR pathway
Subjects
Details
- ISSN :
- 10991263 and 0260437X
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Journal of Applied Toxicology
- Accession number :
- edsair.doi.dedup.....8c5d10984439680a5d21854a0687b4bf