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

Autor(es)

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.

• Tipo de documento: Artigo Científico
• Fonte: Chemico-Biological Interactions; v. 406, p. 12-pg., 2024-11-29.

Resumo

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)

• Processo FAPESP: 18/24814-0 - Metabolômica in vitro de nanopartículas lipídicas funcionais carreadas com anestésico local
• Beneficiário: Gustavo Henrique Rodrigues da Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado
• Processo FAPESP: 23/00229-0 - Papéis fisiopatológicos da NAD(P)+ transidrogenase mitocondrial
• Beneficiário: Roger Frigério Castilho
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/25372-0 - Desenvolvimento de carreadores lipídicos nanoestruturados para encapsulação de anestésicos locais processados em matrizes biopoliméricas para aplicação tópica em mucosa oral
• Beneficiário: Lígia Nunes de Morais Ribeiro
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado