Dexamethasone attenuated bupivacaine-induced neuron injury in vitro through a threonine-serine protein kinase B-dependent mechanism.
Bupivacaine is one of the amide type local anesthetics and is widely used for epidural anesthesia and blockade of nerves. Bupivacaine administration locally could result in neuron injury showing transient neurologic symptoms. Dexamethasone is a synthetic glucocorticoid and may exert cytoprotective properties against damage induced by some stimuli. In the present study, we evaluated the effects of dexamethasone on bupivacaine-induced toxicity in mouse neuroblastoma N2a cells. N2a cells were exposed to bupivacaine in the presence or absence of dexamethasone. After treatment, the cell viability, nuclear condensation, and lactate dehydrogenase levels were evaluated. Mitochondrial potential and Akt (threonine-serine protein kinase B) activation were also examined. In a separate experiment, we examined the effect of Akt inhibition by triciribine on cell viability following dexamethasone treatment. We also investigated whether dexamethasone could prevent lidocaine-induced neurotoxicity. Treatment of N2a cells with bupivacaine resulted in significant cell injury as evidenced by morphological changes, LDH leakage, and nuclear condensation. Pretreatment of the cells with dexamethasone significantly attenuated bupivacaine- and lidocaine-induced cell injury. Dexamethasone treatment prevented the decline of mitochondrial potential caused by bupivacaine and increased the levels of Akt phosphorylation. Importantly, pharmacological inhibition of Akt abolished the protective effect of dexamethasone against bupivacaine-induced cell injury. Our data suggest that pretreatment of neuroblastoma cells with dexamethasone exerts a protective effect on bupivacaine-induced neuronal cell injury. The mechanisms involve activating the Akt signaling pathway.
Ma
R
R
Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China.
Wang
X
X
Lu
C
C
Li
C
C
Cheng
Y
Y
Ding
G
G
Liu
L
L
Ding
Z
Z
D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000633:toxicity*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction
D000779:Anesthetics, Local; D005938:Glucocorticoids; D018696:Neuroprotective Agents; D003907:Dexamethasone; D008012:Lidocaine; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt; D002045:Bupivacaine