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

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 1H 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.

Mitochondrial Dysfunction Was Involved in Decabromodiphenyl Ethane-Induced Glucolipid Metabolism Disorders and Neurotoxicity in Zebrafish Larvae

“…Mitochondria are commonly referred to as energy factories, responsible for the conversion of nutrients such as glucose, lipids, and amino acids into ATP through the electron transport chain and oxidative phosphorylation . Glucose can be decomposed into pyruvate, which is in turn decarboxylated to acetyl CoA and enters the tricarboxylic acid cycle . Fatty acids, undergoing β oxidation, could also ultimately cleave into acetyl CoA and enter the tricarboxylic acid cycle .…”

“…61 Glucose can be decomposed into pyruvate, which is in turn decarboxylated to acetyl CoA and enters the tricarboxylic acid cycle. 62 Fatty acids, undergoing β oxidation, could also ultimately cleave into acetyl CoA and enter the tricarboxylic acid cycle. 63 Hence, the alleviated glycolipid disorders could be, at least partially, related with recovered impairment of RCC I (a membranebound component of the tricarboxylic acid cycle 64 ), RCC IV (a rate-limiting enzyme for ATP synthesis 65 ), and RCC V (another key enzyme for ATP production).…”

Deep simulated annealing for the discovery of novel dental anesthetics with local anesthesia and anti-inflammatory properties

“…Our analysis also showed that conformational restriction was crucial for improving the binding on Na V 1.7 and Na V 1.8, but not of Na V 1.5. In addition, we explored the modifications of the methyl ester, which is known to undergo rapid hydrolysis 35 . Remarkably, as the steric hindrance increased up to n- propyl ( AT-28 ), binding to Na V 1.7 improved before decreasing again.…”

A Deep Learning Approach to Analyze NMR Spectra of SH-SY5Y Cells for Alzheimer’s Disease Diagnosis

“…NMR metabolomics allows to identify the entire metabolite spectrum in many biological fluids and cellular extract/medium, obtaining a metabolic fingerprint (metabolic profile) that characterizes the healthy or diseased state [7]. NMR spectroscopy, compared to other techniques, has the advantage of being rapid and not requiring a particular treatment of the samples [8].…”