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Protein & Peptide Letters

Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Neuroprotective Effect of Dexmedetomidine Pretreatment on Sevoflurane- Initiated Neurotoxicity Via the Mir-204-5p/SOX4 Axis

Author(s): Run Wang, Pengfei Liu, Fan Li and Hui Qiao*

Volume 30, Issue 7, 2023

Published on: 03 July, 2023

Page: [608 - 618] Pages: 11

DOI: 10.2174/0929866530666230530164913

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Abstract

Background: Sevoflurane (Sev) is a type of volatile anesthetic commonly used in clinic practices and can initiate long-term neurotoxicity, while dexmedetomidine (Dex) possesses a neuroprotective function in multiple neurological disorders.

Objective: This work expounded on the function of Dex pretreatment in Sev-initiated neurotoxicity.

Methods: At first, human neuroblastoma cells (SK-N-SH cells) were treated with different concentrations of Sev or Dex, followed by the cell counting kit (CCK)-8 assay to decide the appropriate concentrations of Sev or Dex. Cell viability, lactate dehydrogenase (LDH) productions, and apoptotic rate of SK-N-SH cells were examined by the CCK-8 assay, LDH cytotoxicity kit, and flow cytometry assay in sequence. Further, reactive oxygen species (ROS) levels and proinflammatory cytokine contents were examined by the ROS assay kit and the enzyme-linked immunosorbent assay kits. The expression patterns of microRNA (miR)-204-5p and SRY-box transcription factor 4 (SOX4) in SK-N-SH cells were measured by real-time quantitative polymerase chain reaction or Western blotting. The binding relationship between miR-204-5p and SOX4 was confirmed by the dual-luciferase assay. After transfection of miR-204-5p mimics or SOX4 siRNA, the role of the miR-204-5p/SOX4 axis in Sev-initiated neurotoxicity was detected.

Results: Sev treatment reduced SK-N-SH cell viability in a concentration-dependent manner, and Dex pretreatment diminished Sev-initiated neurotoxicity. Mechanically, Dex pretreatment limited Sevinduced upregulation of miR-204-5p and further increased SOX4 expression levels. miR-204-5p upregulation or SOX4 knockdown averted the neuroprotection function of Dex pretreatment in Sevinitiated neurotoxicity.

Conclusion: Dex pretreatment decreased miR-204-5p expression levels and upregulated SOX4 expression levels, palliating Sev-initiated neurotoxicity.

Keywords: Neurotoxicity, sevoflurane, SK-N-SH cells, dexmedetomidine, miR-204-5p, neuroinflammation.

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Graphical Abstract

Graphical abstract illustrating key findings of the study

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