Dexamethasone attenuated bupivacaine-induced neuron injury in vitro through a threonine–serine protein kinase B-dependent mechanism

Ma, Rong; Wang, X.; Lu, Chuncheng; Li, C.; Cheng, Yusheng; Ding, Guoxian; Liu, L.; Ding, Zhengnian

doi:10.1016/j.neuroscience.2009.12.049

Cited by 97 publications

(75 citation statements)

References 46 publications

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“…SH‐SY5Y cells were treated with bupivacaine, lidocaine, tetracaine, procaine and ropivacaine at different dosages according to the previous studies 7, 18, 19, 21, 22, 23, 24. Cell viability was evaluated by MTT assay 24 hrs after LAs challenge.…”

Section: Resultsmentioning

confidence: 99%

“…To address these questions, we treated human neuroblastoma SH‐SY5Y cells with both lipid LAs (procaine and tetracaine) and amide LAs (bupivacaine, lidocaine and ropivacaine) at previously described dosages 18, 19, 21, 22, 23, 24. The results showed that all the examined LAs up‐regulated autophagic process and inhibited tuberin/mTOR/p70S6K signalling in neuronal cells.…”

Section: Introductionmentioning

confidence: 99%

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Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity

Xiong

Kong

Dai

et al. 2016

J Cellular Molecular Medi

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The local anaesthetics (LAs) are widely used for peripheral nerve blocks, epidural anaesthesia, spinal anaesthesia and pain management. However, exposure to LAs for long duration or at high dosage can provoke potential neuronal damages. Autophagy is an intracellular bulk degradation process for proteins and organelles. However, both the effects of LAs on autophagy in neuronal cells and the effects of autophagy on LAs neurotoxicity are not clear. To answer these questions, both lipid LAs (procaine and tetracaine) and amide LAs (bupivacaine, lidocaine and ropivacaine) were administrated to human neuroblastoma SH‐SY5Y cells. Neurotoxicity was evaluated by MTT assay, morphological alterations and median death dosage. Autophagic flux was estimated by autolysosome formation (dual fluorescence LC3 assay), LC3‐II generation and p62 protein degradation (immunoblotting). Signalling alterations were examined by immunoblotting analysis. Inhibition of autophagy was achieved by transfection with beclin‐1 siRNA. We observed that LAs decreased cell viability in a dose‐dependent manner. The neurotoxicity of LAs was tetracaine > bupivacaine > ropivacaine > procaine > lidocaine. LAs increased autophagic flux, as reflected by increases in autolysosome formation and LC3‐II generation, and decrease in p62 levels. Moreover, LAs inhibited tuberin/mTOR/p70S6K signalling, a negative regulator of autophagy activation. Most importantly, autophagy inhibition by beclin‐1 knockdown exacerbated the LAs‐provoked cell damage. Our data suggest that autophagic flux was up‐regulated by LAs through inhibition of tuberin/mTOR/p70S6K signalling, and autophagy activation served as a protective mechanism against LAs neurotoxicity. Therefore, autophagy manipulation could be an alternative therapeutic intervention to prevent LAs‐induced neuronal damage.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity

Xiong

Kong

Dai

et al. 2016

J Cellular Molecular Medi

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“…Although caution is warranted, animal studies have provided encouraging results, concluding that neurological injury is absent [7,14,57]. During in-vitro studies, Ma et al demonstrated a potential protective effect of dexamethasone against local anaesthetic-induced cell injury [58] and a series of 2000 intrathecal injections of 8 mg dexamethasone for the treatment of post-traumatic visual disturbance in 200 patients failed to demonstrate any neurological sequelae [59]. Nevertheless, clinicians must be aware that perineural dexamethasone represents off-label use and solutions free of neurotoxic preservatives should be used [60,61].…”

Section: Discussionmentioning

confidence: 99%

A systematic review and meta‐analysis of perineural dexamethasone for peripheral nerve blocks

2014

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SummaryWe systematically reviewed the safety and efficacy of perineural dexamethasone as an adjunct for peripheral nerve blockade in 29 controlled trials of 1695 participants. We grouped trials by the duration of local anaesthetic action (short-or medium-vs long-term). Dexamethasone increased the mean (95% CI) duration of analgesia by 233 (172-295) min when injected with short-or medium-term action local anaesthetics and by 488 (419-557) min when injected with long-term action local anaesthetics, p < 0.00001 for both. However, these results should be interpreted with caution due to the extreme heterogeneity of results, with I 2 exceeding 90% for both analyses. Meta-regression did not show an interaction between dose of perineural dexamethasone (4-10 mg) and duration of analgesia (r 2 = 0.02, p = 0.54). There were no differences between 4 and 8 mg dexamethasone on subgroup analysis.

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“… Por otro lado, existen estudios 33,34,36 que defienden la teoría de que la dexametasona atenúa los mediadores de la respuesta inflamatoria producida por la cirugía, al disminuir la descarga neuronal ectópica e inhibir los canales de potasio dependientes de las fibras C-Nociceptivas.…”

Section: Efecto Analgésico De La Dexametasona Aplicada a Nivel Perineunclassified

“…Sin embargo, la dexametasona prolonga el efecto analgésico en bloqueos nerviosos del plexo braquial [22][23][24][25][26][27][28][29][30] y del nervio ciático 31,32 sin efectos secundarios. Esta propiedad parece ser debida a que por un lado, la dexametasona atenúa los mediadores de la respuesta inflamatoria producida por la cirugía, al disminuir la descarga neuronal ectópica e inhibir los canales de potasio dependientes de las fibras C-Nociceptivas [33][34][35][36] , y por otro lado a su poder de vasoconstricción 31 , disminuyendo por tanto la absorción de los AL.…”

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Eficacia analgésica de una dosis única de dexametasona perineural en el bloqueo ecoguiado del nervio femoral en cirugía de prótesis total de rodilla

Morales-Muñoz

Sánchez-Ramos

Díaz-Lara

et al. 2017

Revista Española de Anestesiología y Reanimación

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Dexamethasone attenuated bupivacaine-induced neuron injury in vitro through a threonine–serine protein kinase B-dependent mechanism

Cited by 97 publications

References 46 publications

Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity

Autophagy activated by tuberin/mTOR/p70S6K suppression is a protective mechanism against local anaesthetics neurotoxicity

A systematic review and meta‐analysis of perineural dexamethasone for peripheral nerve blocks

Eficacia analgésica de una dosis única de dexametasona perineural en el bloqueo ecoguiado del nervio femoral en cirugía de prótesis total de rodilla

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