Articaine: The Less Neurotoxic Dental Anesthetic In Human Neuroblastoma Cells

Method:  Undifferentiated SH-SY5Y cells were seeded in supplemented DMEM. After confluences, LA and controls were incubated for 20 minutes. Each assay was run in three independent experiments. Metabolic activity of viable cells was assessed by WST-1 assay followed by spectrometry quantification. LD₅₀ is determined by extrapolation of curve response. Results were expressed as mean +/- SD. The relative toxicity of anesthetics was evaluated with anesthetics LD₅₀/lidocaine LD₅₀ ratio using lidocaine as the reference. Statistical analysis was performed (p<0.05). Moreover, microscopic pictures illustrated LA effects.

Result:  As expected, all LA induced cell death in a concentration-dependant manner. The LD₅₀ of bupivacaine, lidocaine, prilocaine, mepivacaine, articaine and ropivacaine were respectively 1 mM, 3.5 mM, 4.2 mM, 5.5 mM, 8.7 mM and 12.6 mM after 20 min of incubation on SH-SY5Y. Ropivacaine and articaine LD₅₀ were significantly higher than bupivacaine, lidocaine and prilocaine LD₅₀. No significant difference was obtained between lidocaine, prilocaine and mepivacaine LD₅₀. Bupivacaine LD50 was significantly lower compared to all LAs. The ratios LD₅₀ of ropivacaine/lidocaine, articaine/lidocaine, mepivacaine/lidocaine, prilocaine/lidocaine and bupivacaine/lidocaine were respectively equal to 3.6, 2.4, 1.5, 1.2 and 0.3.

Conclusion: The human neuroblastoma cell line, SH-SY5Y, is a suitable model to test the LA’s neurotoxicity. LD₅₀ rank LA from high to low toxicity: bupivacaine > lidocaine ≈ prilocaine > mepivacaine > articaine ≈ ropivacaine. Consequently, three groups of local anesthetics were identified 1: ropivacaine, articaine; 2: mepivacaine, prilocaine, lidocaine; 3: bupivacaine in terms of toxicity.

Amongst dental anesthetics, articaine is the less neurotoxic in SH-SY5Y cells.