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

Author(s)

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

• Document type: Journal article
• Source: METABOLITES; v. 12, n. 7, p. 17-pg., 2022-07-01.

Abstract

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)

• FAPESP's process: 14/14457-5 - Lipid-based nanocarriers (SLN/NLC and remote-loading liposomes) used to improve the upload and potency of local anesthetics
• Grantee: Eneida de Paula
• Support Opportunities: Research Projects - Thematic Grants
• 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: 19/17784-0 - Plasma pharmacokinetics and tissue biodistribution of lipid-based nanoformulations
• Grantee: Eneida de Paula
• Support Opportunities: Regular Research Grants