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Benzodiazepines safeguards nerve cells from the toxicity of lidocaine via miR-133a-3p/EGFR pathway.
- Source :
-
Transplant Immunology . Apr2022, Vol. 71, p1-7. 7p. - Publication Year :
- 2022
-
Abstract
- Background Lidocaine was an anesthetic commonly used for analgesia, but the neurotoxicity could not be ignored. However, benzodiazepines could alleviate the toxicity when combined with other drugs. Purpose To explore the molecular mechanism of benzodiazepines in protecting nerve cells after the induction of lidocaine. Methods PC12 cells were induced by lidocaine (0 mM, 0.1 mM, 0.5 mM and 1 mM) first and then treated by benzodiazepines (0 μM–200 μM). RT-qPCR assays measured RNA expressions of epidermal growth factor receptor (EGFR) and microRNA-133a-3p (miR-133a-3p) in PC12 cell line, respectively. Western blot was for protein detections of EGFR and caspase-3. Flow cytometry assay assessed apoptosis and cellular viability was validated via Cell Counting Kit-8 (CCK-8) test. Bioinformatics analysis predicted the potential link between miR-133a-3p and EGFR and the binding was verified using the Dual luciferase reporter experiment. Results Benzodiazepines increased cellular viability of PC12 cells up to 100 μM while suppressed viability between 100 and 200 μM. Benzodiazepines (0 μM, 10 μM, 50 μM and 100 μM) did not regulate PC12 cell viability but promoted the viability of lidocaine-treated PC12 cells. Lidocaine downregulated miR-133a-3p RNA expression but facilitated EGFR mRNA expression, which was reversed after treated by benzodiazepines. MiR-133a-3p targeted and negatively regulated EGFR expressions in mRNA and protein levels. Furthermore, miR-133a-3p inhibitor and overexpressed EGFR transfection both restrained the decreased PC12 cell viability and prompted cell apoptosis caused by benzodiazepines. Conclusion Benzodiazepines restrained lidocaine-induced toxicity in PC12 cells which secured viability and reduced apoptosis via miR-133a-3p/EGFR pathway. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09663274
- Volume :
- 71
- Database :
- Academic Search Index
- Journal :
- Transplant Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 163965333
- Full Text :
- https://doi.org/10.1016/j.trim.2021.101510