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.
palavras-chave
DIFFERENT LOCAL-ANESTHETICS; NEUROBLASTOMA-CELLS; PROLINE OXIDASE; ACTIVATION; CYTOTOXICITY; ENZYMES; STRESS; INJURY; DAMAGE; BLOCK
categoria
Biochemistry & Molecular Biology
autores
da Silva, GHR; Mendes, LF; de Carvalho, FV; de Paula, E; Duarte, IF
nossos autores
Gustavo Henrique Rodrigues da Silva
Estudante de doutoramento
Iola Melissa Fernandes Duarte
Investigador Principal
Luís Filipe Figueiredo Mendes
Estudante de doutoramentoProjectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
agradecimentos
This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020, UIDP/50011/2020 and LA/P/0006/2020, and financed by national funds through the FCT/MEC (PIDDAC). The NMR spectrometer is part of the National NMR Network (PTNMR), partially supported by Infrastructure Project N degrees 022161 (cofinanced by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC). The authors also thank Sao Paulo research foundation, FAPESP (G.H.R.S. scholarship #18/24814-0; E.P. grants #14/14457-5, 19/17784-0).