TY - JOUR
T1 - Lipophilicity but not stereospecificity is a major determinant of local anaesthetic-induced cytotoxicity in human T-lymphoma cells
AU - Werdehausen, Robert
AU - Braun, Sebastian
AU - Fazeli, Sepideh
AU - Hermanns, Henning
AU - Hollmann, Markus W.
AU - Bauer, Inge
AU - Stevens, Markus F.
PY - 2012
Y1 - 2012
N2 - Background and objectives Local neurotoxicity of local anaesthetics is a well known phenomenon which is determined by lipophilicity. Recent reports have indicated the relevance of local anaesthetic-induced cytotoxicity also in nonneuronal tissues. This study re-evaluates the role of lipophilicity in local anaesthetic cytotoxicity in nonneuronal cells. In addition, the toxicities of pipecoloxylidine S(-) enantiomers were investigated. Methods Local anaesthetic-induced cytotoxicity was investigated in vitro in T-lymphoma cells (Jurkat). Cells were incubated with each of eight different local anaesthetics, two esters and six amides. Annexin V-fluorescein isothiocyanate and 7-aminoactinomycin D double staining followed by flow cytometry were used to investigate the fraction of early apoptotic cells as well as the overall cell death. The concentrations leading to 50% cell death (LC(50)) were calculated and compared. In a second step, we compared the toxicities of S(-) bupivacaine and the racemate as well as R(R) and S(-) ropivacaine. Results Concentration-dependent cytotoxicity was observed for all investigated local anaesthetics. Apoptosis was seen at low concentrations, whereas necrosis was observed at higher concentrations. LC(50) values of the different local anaesthetics yielded the following decreasing order of toxicity: tetracaine, bupivacaine, ropivacaine, prilocaine, procaine, lidocaine, articaine and mepivacaine. Toxicity correlated with octanol/buffer partition coefficients, but was independent of the ester or amide linkage. There was no effect of stereoisomerism on apoptosis and necrosis. Conclusion Moderate correlations for cytotoxicity with lipophilicity and clinical potency of local anaesthetics can be found in nonneuronal cells that are less than those reported previously with neuronal cells. Structural factors such as ester or amide linkage or stereospecificity do not have any influence on cytotoxicity. Although S(-) enantiomers may be advantageous with regard to systemic toxicity, they have no advantage in respect of local cytotoxicity in vitro. Eur J Anaesthesiol 2012;29:35-41 Published online 19 October 2011
AB - Background and objectives Local neurotoxicity of local anaesthetics is a well known phenomenon which is determined by lipophilicity. Recent reports have indicated the relevance of local anaesthetic-induced cytotoxicity also in nonneuronal tissues. This study re-evaluates the role of lipophilicity in local anaesthetic cytotoxicity in nonneuronal cells. In addition, the toxicities of pipecoloxylidine S(-) enantiomers were investigated. Methods Local anaesthetic-induced cytotoxicity was investigated in vitro in T-lymphoma cells (Jurkat). Cells were incubated with each of eight different local anaesthetics, two esters and six amides. Annexin V-fluorescein isothiocyanate and 7-aminoactinomycin D double staining followed by flow cytometry were used to investigate the fraction of early apoptotic cells as well as the overall cell death. The concentrations leading to 50% cell death (LC(50)) were calculated and compared. In a second step, we compared the toxicities of S(-) bupivacaine and the racemate as well as R(R) and S(-) ropivacaine. Results Concentration-dependent cytotoxicity was observed for all investigated local anaesthetics. Apoptosis was seen at low concentrations, whereas necrosis was observed at higher concentrations. LC(50) values of the different local anaesthetics yielded the following decreasing order of toxicity: tetracaine, bupivacaine, ropivacaine, prilocaine, procaine, lidocaine, articaine and mepivacaine. Toxicity correlated with octanol/buffer partition coefficients, but was independent of the ester or amide linkage. There was no effect of stereoisomerism on apoptosis and necrosis. Conclusion Moderate correlations for cytotoxicity with lipophilicity and clinical potency of local anaesthetics can be found in nonneuronal cells that are less than those reported previously with neuronal cells. Structural factors such as ester or amide linkage or stereospecificity do not have any influence on cytotoxicity. Although S(-) enantiomers may be advantageous with regard to systemic toxicity, they have no advantage in respect of local cytotoxicity in vitro. Eur J Anaesthesiol 2012;29:35-41 Published online 19 October 2011
U2 - https://doi.org/10.1097/EJA.0b013e32834cd6c4
DO - https://doi.org/10.1097/EJA.0b013e32834cd6c4
M3 - Article
C2 - 22012177
SN - 0265-0215
VL - 29
SP - 35
EP - 41
JO - European Journal of Anaesthesiology
JF - European Journal of Anaesthesiology
IS - 1
ER -