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Hirsutanol A exhibits neuroprotective activities against sevoflurane-induced neurotoxicity in aged rats.
- Source :
-
Anatomical record (Hoboken, N.J. : 2007) [Anat Rec (Hoboken)] 2021 Mar; Vol. 304 (3), pp. 591-601. Date of Electronic Publication: 2020 Aug 02. - Publication Year :
- 2021
-
Abstract
- The neurotoxicity of the inhaled anesthetic, sevoflurane, has been documented in a number of studies. In this study, we conducted experiments to investigate whether Hirsutanol A (HA), a sesquiterpene compound from the fungus, Chondrostereum sp., can provide protection from sevoflurane-induced neurological toxicity in aged rats, and analyzed the underlying mechanisms. The cognitive dysfunction of rats following sevoflurane exposure was evaluated by behavioral tests. The neuronal cell survival was determined by Nissl staining. In addition, human neuroblastoma H4 cells were exposed to sevoflurane to establish an in vitro model. Apoptotic marker expression in hippocampal tissue was determined by western blotting. Cell apoptosis in vitro was also examined by TUNEL assay and flow cytometry. The expression and translocation of Nrf2 were examined by both western blot and immunofluorescence staining. Our results show that HA significantly attenuated sevoflurane-induced cognitive impairment in aged rats. In addition, HA treatment decreased sevoflurane-induced neuronal apoptosis in the hippocampus and alleviated Aβ accumulation. Our results also show that the neuroprotective effect of HA is associated with the activation of Nrf2 signaling. Human neuroblastoma H4 cells were used as a model to examine the protective activity of HA against sevoflurane-induced neurotoxicity. In addition, our results show that the inhibition of Nrf2 by a specific inhibitor or targeting siRNA significantly compromises the attenuating effect of HA on sevoflurane-induced cell apoptosis and Aβ accumulation. Our results suggest that HA may function as a neuroprotective agent against sevoflurane-induced neurotoxicity.<br /> (© 2020 American Association for Anatomy.)
- Subjects :
- Amyloid beta-Peptides metabolism
Animals
Apoptosis drug effects
Cell Line, Tumor
Cognitive Dysfunction chemically induced
Cognitive Dysfunction metabolism
Hippocampus metabolism
Humans
Male
Maze Learning drug effects
Neurons drug effects
Neurons metabolism
Neuroprotective Agents therapeutic use
Rats
Rats, Sprague-Dawley
Sesquiterpenes therapeutic use
Signal Transduction drug effects
Anesthetics, Inhalation adverse effects
Cognitive Dysfunction drug therapy
Hippocampus drug effects
Neuroprotective Agents pharmacology
Sesquiterpenes pharmacology
Sevoflurane adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1932-8494
- Volume :
- 304
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Anatomical record (Hoboken, N.J. : 2007)
- Publication Type :
- Academic Journal
- Accession number :
- 32536020
- Full Text :
- https://doi.org/10.1002/ar.24473