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image of Lidocaine Induces Neurotoxicity by Activating the CaMKII and p38 MAPK Signaling Pathways through an Increase in Intracellular Calcium Ions

Abstract

Background

Lidocaine is extensively utilized as an anesthetic in clinical settings; however, it has demonstrated significant neurotoxicity when administered for spinal anesthesia. The specific mechanisms underlying lidocaine-induced neurotoxicity are poorly understood.

Objective

This study aimed to investigate the mechanisms through which lidocaine induces neurotoxicity, focusing on its effects on intracellular calcium release and the activation of CaMKII and MAPKs pathways, as well as to evaluate the potential protective effects of cilnidipine.

Methods

The investigation has employed both cell models and mouse models to conduct the experiments. Neuronal cell viability has been assessed following lidocaine treatment, and neurological function has been evaluated in mice after intrathecal injection of lidocaine. Intracellular calcium levels, CaMKII activation, and the phosphorylation of p38 and p65 have been measured in cultured hippocampal neuronal cells and mouse brain tissues. The effects of the calcium channel blocker cilnidipine on these parameters have also been examined.

Results

Lidocaine treatment led to a reduction in cell viability in cultured neuronal cells and induced neurological dysfunction in mice. It increased intracellular Ca2+ levels and activated CaMKII in both cultured neuronal cells and mouse brain tissues. Lidocaine also elevated the phosphorylation levels of p38 and p65 in neuronal cells. These effects have been suppressed by cilnidipine, indicating a calcium-dependent mechanism.

Conclusion

This study suggests that lidocaine induces neurotoxicity through a calcium-dependent activation of CaMKII and MAPK pathways, leading to neuronal apoptosis and dysfunction. Cilnidipine has been found to exhibit promise as a protective agent against lidocaine-induced neurotoxicity.

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2024-11-22
2024-12-26

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Lidocaine Induces Neurotoxicity by Activating the CaMKII and p38 MAPK Signaling Pathways through an Increase in Intracellular Calcium Ions
Bentham Science Publishers ; https://doi.org/10.2174/0115701808355819241118115155
/content/journals/lddd/10.2174/0115701808355819241118115155
/content/journals/lddd/10.2174/0115701808355819241118115155
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  • Article Type:     Research Article
Keywords: cilnidipine ; calcium ; p38 MAPK ; neurotoxicity ; Lidocaine ; CaMKII

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