Protective effect of quercetin on bupivacaine-induced neurotoxicity via T-type calcium channel inhibition

Purpose: To determine the effect of quercetin on bupivacaine-induced neurotoxicity and to investigate the mechanisms involved.
Methods: Cultured SH-SY5Y cells were divided into five treatment groups: control group with no drug, bupivacaine treatment group, quercetin group, bupivacaine--quercetin combination treatment group, and bupivacaine-mibefradil combination treatment group. Cell morphology in each group was examined by microscopy while cell viability was assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-tetrazolium bromide (MTT) assay after 24 h incubation. Cytosolic calcium ion concentration was determined by flow cytometry while Cav3.1 protein expression was evaluated by western blot.
Results: Quercetin (50 μM) significantly (p < 0.05) protected SH-SYS5 cells from bupivacaine-induced cell apoptosis and also significantly reduced intracellular calcium ion concentration (p < 0.01) by approximately 40 %. Cav3.1 protein expression was normalized following quercetin treatment.
Conclusion: These results show that quercetin reduces the neurotoxicity induced by bupivacaine, possibly through inhibition of T-type calcium channel. This finding implies a novel mechanism for neuroprotective effect of quercetin, and its potential for treating toxicity arising from the use of local anesthetic agents.

Keywords
Quercetin; Bupivacaine; Local anaesthetic; Neuroprotection; Neurotoxicity; T-type calcium channel