Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells

Autor(es)

Rodrigues da Silva, Gustavo H. ; Mendes, Luis F. ; de Carvalho, Fabiola, V ; de Paula, Eneida ; Duarte, Iola F.

• Tipo de documento: Artigo Científico
• Fonte: METABOLITES; v. 12, n. 7, p. 17-pg., 2022-07-01.

Resumo

Articaine (ATC) and lidocaine (LDC) are the local anesthetics (LAs) currently most employed in dentistry. Cases of paresthesia, reported more frequently for ATC, have raised concerns about their potential neurotoxicity, calling for further investigation of their biological effects in neuronal cells. In this work, the impact of ATC and LDC on the metabolism of SH-SY5Y cells was investigated through H-1 NMR metabolomics. For each LA, in vitro cultured cells were exposed to concentrations causing 10 and 50% reductions in cell viability, and their metabolic intracellular and extracellular profiles were characterized. Most effects were common to ATC and LDC, although with varying magnitudes. The metabolic variations elicited by the two LAs suggested (i) downregulation of glycolysis and of glucose-dependent pathways (e.g., one-carbon metabolism and hexosamine biosynthetic pathway), (ii) disturbance of branched chain amino acids (BCAA) catabolism, (iii) downregulation of TCA cycle anaplerotic fueling and activation of alternative energy producing pathways, (iv) interference with choline metabolism and (v) lipid droplet build-up. Interestingly, LDC had a greater impact on membrane phospholipid turnover, as suggested by higher phosphatidylcholine to phosphocholine conversion. Moreover, LDC elicited an increase in triglycerides, whereas cholesteryl esters accumulated in ATC-exposed cells, suggesting a different composition and handling of lipid droplets. (AU)

• Processo FAPESP: 14/14457-5 - Carreadores baseados em lipídios (SLN/NLC e lipossomas com gradiente iônico) como estratégia para aumentar a encapsulação e a potência de anestésicos locais
• Beneficiário: Eneida de Paula
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• 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: 19/17784-0 - Análise farmacocinética e de distribuição local no tecido-alvo de fármacos encapsulados em sistemas carreadores baseados em lipídios
• Beneficiário: Eneida de Paula
• Modalidade de apoio: Auxílio à Pesquisa - Regular