Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells
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....
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MDPI AG
2022-06-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/12/7/581 |
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| author | Gustavo H. Rodrigues da Silva Luís F. Mendes Fabíola V. de Carvalho Eneida de Paula Iola F. Duarte |
| author_facet | Gustavo H. Rodrigues da Silva Luís F. Mendes Fabíola V. de Carvalho Eneida de Paula Iola F. Duarte |
| author_sort | Gustavo H. Rodrigues da Silva |
| collection | DOAJ |
| description | 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 <sup>1</sup>H 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. |
| first_indexed | 2024-03-09T13:24:29Z |
| format | Article |
| id | doaj.art-94ff21e2d50d499eb994d296df2e527a |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-09T13:24:29Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-94ff21e2d50d499eb994d296df2e527a2023-11-30T21:26:28ZengMDPI AGMetabolites2218-19892022-06-0112758110.3390/metabo12070581Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal CellsGustavo H. Rodrigues da Silva0Luís F. Mendes1Fabíola V. de Carvalho2Eneida de Paula3Iola F. Duarte4CICECO—Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalCICECO—Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-862, SP, BrazilDepartment of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas 13083-862, SP, BrazilCICECO—Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, PortugalArticaine (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 <sup>1</sup>H 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.https://www.mdpi.com/2218-1989/12/7/581local anestheticsarticaine and lidocainetoxicometabolomicsneuronal cellsneurotoxicity |
| spellingShingle | Gustavo H. Rodrigues da Silva Luís F. Mendes Fabíola V. de Carvalho Eneida de Paula Iola F. Duarte Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells Metabolites local anesthetics articaine and lidocaine toxicometabolomics neuronal cells neurotoxicity |
| title | Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells |
| title_full | Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells |
| title_fullStr | Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells |
| title_full_unstemmed | Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells |
| title_short | Comparative Metabolomics Study of the Impact of Articaine and Lidocaine on the Metabolism of SH-SY5Y Neuronal Cells |
| title_sort | comparative metabolomics study of the impact of articaine and lidocaine on the metabolism of sh sy5y neuronal cells |
| topic | local anesthetics articaine and lidocaine toxicometabolomics neuronal cells neurotoxicity |
| url | https://www.mdpi.com/2218-1989/12/7/581 |
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