The mechanisms of local anesthetics toxicity by discrimination between apoptosis and necrosis

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Many studies have indicated that local anesthetics are cytotoxic and can induce apoptosis; however, the types of local anesthetics and the induction rates of apoptosis remain unclear. The aim of this study was to clarify the local anesthetics that induce apoptosis or necrosis and their induction-related factors. Methods : Lidocaine, mepivacaine, bupivacaine, ropivacaine, tetracaine, dibucaine, procaine, and QX-314 were evaluated for apoptosis and necrosis in HL-60 human leukemia cell lines. Apoptosis and necrosis were analyzed by double-staining assay with propidium iodide (PI) and annexin-V and were measured by flow cytometry (FACS). DNA fragmentation was used for the analysis of apoptosis.Conclusion : The results indicate that local anesthetics with high lipophilicity are highly toxic and induce mainly necrosis, while local anesthetics with low pKa induce more apoptosis.