Dose-Response (Mar 2022)

Osthole-Mediated Inhibition of Neurotoxicity Induced by Ropivacaine via Amplification of the Cyclic Adenosine Monophosphate Signaling Pathway

  • WeiBing Wang,
  • Hui Zhou,
  • LaiBao Sun,
  • MeiNa Li,
  • FengJiao Gao,
  • AiJiao Sun,
  • XueNong Zou

DOI
https://doi.org/10.1177/15593258221088092
Journal volume & issue
Vol. 20

Abstract

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Background Ropivacaine is widely used for clinical anesthesia and postoperative analgesia. However, the neurotoxicity induced by ropivacaine in a concentration- and duration-dependent manner, and it is difficult to prevent neurotoxicity. Osthole inhibits phosphodiesterase-4 activity by binding to its catalytic site to prevent cAMP hydrolysis. The aim of this present study is to explore the precise molecular mechanism of osthole-mediated inhibition of neurotoxicity induced by ropivacaine. Methods: SH-SY5Y cell viability and apoptosis were measured in different concentration and duration. Protein concentration was determined in each signaling pathway. The molecular mechanism of osthole-mediated inhibition of ropivacaine-caused neurotoxicity was evaluated. Results The study demonstrated that osthole inhibits SH-SY5Y cells neurotoxicity in a duration- and concentration-dependent manner. Moreover, ropivacaine significantly increased the expression of caspase-3 by promoting the phosphorylation of p38. Osthole-induced upregulation of cAMP activated cAMP-dependent signaling pathway, sequentially leading to elevated cyclic nucleotide response element-binding protein levels, which inhibits P38-dependent signaling and decreases apoptosis of SH-SY5Y. Conclusions This study display the evidence confirmed the molecular mechanism by which osthole amplification of cAMP-dependent signaling pathway, and overexpression of cyclic nucleotide response element-binding protein inhibits P38-dependent signaling and decreases ropivacaine-induced SH-SY5Y apoptosis.