Schwann cells exposed to articaine display distinct toxic pathways compared to lidocaine

Author(s)

Silva, Gustavo H. Rodrigues da ; Mendes, Luis F. ; Geronimo, Gabriela ; de Moura, Ludmilla D. ; Ruas, Juliana S. ; Castilho, Roger F. ; Cordeiro, Helon G. ; Ferreira, Carmen, V ; de Paula, Eneida ; Duarte, Iola F.

• Document type: Journal article
• Source: Chemico-Biological Interactions; v. 406, p. 12-pg., 2024-11-29.

Abstract

Articaine (ATC) has emerged as one of the most popular local anesthetics (LA) in dental clinics, despite its relatively recent introduction to the market. As a member of the amino-amide class of LA, ATC possesses unique features, including a thiophene ring and an ester group, which allow for its use at higher clinical concentrations. However, reports have indicated a higher incidence of paresthesia associated with ATC, though the underlying cause of this effect remains unclear. To investigate this further, we conducted an extracellular metabolic flux analysis and an NMR-based metabolomics study of ATC effects on Schwann cells- a type of glial cell found in the peripheral nervous system- in comparison to lidocaine (LDC), the "gold standard" LA in dentistry. The results showed that ATC had a more significant impact on Schwann cell oxygen consumption compared to LDC. Metabolomics profiling of Schwann cells revealed distinct metabolic alterations between the two treatments. Notably, ATC triggered elevated intracellular levels of various amino acids, including leucine, isoleucine, valine, phenylalanine, methionine, histidine, tyrosine, and glycine, which were not observed in LDC-treated Schwann cells. This was consistent with signs of endoplasmic reticulum stress and apoptosis in ATC-treated cells, as detected by protein expression analysis. These findings offer insights into the metabolic and cellular responses elicited by the two anesthetics in Schwann cells, that may help explain the differential toxicity and higher incidence of paresthesia associated with ATC. (AU)

• FAPESP's process: 18/24814-0 - Metabolomics of nanoparticles lipid carriers loaded with local anesthetic in vitro
• Grantee: Gustavo Henrique Rodrigues da Silva
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 23/00229-0 - Pathophysiological roles of mitochondrial NAD(P)+ transhydrogenase
• Grantee: Roger Frigério Castilho
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/25372-0 - Development of nanostructured lipid carriers encapsulating local anesthetics processed biopolymeric matrices for topical application at oral mucosa
• Grantee: Lígia Nunes de Morais Ribeiro
• Support Opportunities: Scholarships in Brazil - Post-Doctoral