The Comparative Cytotoxic Effects of Different Local Anesthetics on a Human Neuroblastoma Cell Line

Malet, Arnaud; Faure, Marie-Odile; Delétage, Nathalie; Pereira, Bruno; Haas, Jerome; Lambert, Grégory

doi:10.1213/ane.0000000000000562

Cited by 59 publications

(55 citation statements)

References 40 publications

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“…5). SH-SY5Y cells of the human neuroblastoma cell line are widely used in cytotoxic research23242728. Because the cytotoxic response is similar to that of human primary neuronal cultures16.…”

Section: Discussionmentioning

confidence: 99%

“…Bupivacaine, an amide-type LA, is commonly used clinically is also frequently studied in neurotoxicology testing172428. Procaine is a classic short-acting ester-type local anaesthetic and has been in use because of its low toxicity172730.…”

Section: Discussionmentioning

confidence: 99%

“…They observed that lidocaine and bupivacaine could activate caspase-3/-7, leading to apoptosis, but their patterns of activation were different27. Because the diffusion of LAs was affected by multiple factors, such as the concentration gradient, the affinity for lipids, and their protein-binding ability and pKa, Malet compared the neurotoxicity of seven LAs in undifferentiated SH-SY5Y cells, taking the physicochemical properties of pKa and lipid water partition coefficient (LWPC) into account28. However, the shortcoming of the previous studies is that none of them comprehensively explored the distinct mechanisms of neurotoxicity of amide- and ester-type drugs, which underscores the significance of our study.…”

Section: Discussionmentioning

confidence: 99%

“…Afterward, Arnaud Malet et al . assessed the neurotoxicity of different LAs on SH-SY5Y cells using the WST-1 method172728. Mete evaluated the neurotoxic effects of four LAs on the mouse neuroblastoma NB2a cell line11.…”

mentioning

confidence: 99%

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Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine

Zhao

et al. 2017

Sci Rep

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Local anaesthetics (LAs) may lead to neurological complications, but the underlying mechanism is still unclear. Many neurotoxicity research studies have examined different LAs, but none have comprehensively explored the distinct mechanisms of neurotoxicity caused by amide- (bupivacaine) and ester- (procaine) type LAs. Here, based on a CCK8 assay, LDH assay, Rhod-2-AM and JC-1 staining, 2′,7′-dichlorohy-drofluorescein diacetate and dihydroethidium probes, an alkaline comet assay, and apoptosis assay, we show that both bupivacaine and procaine significantly induce mitochondrial calcium overload and a decline in the mitochondrial membrane potential as well as overproduction of ROS, DNA damage and apoptosis (P < 0.05). There were no significant differences in mitochondrial injury and apoptosis between the bupivacaine and procaine subgroups (P > 0.05). However, to our surprise, the superoxide anionic level after treatment with bupivacaine, which leads to more severe DNA damage, was higher than the level after treatment with procaine, while procaine produced more peroxidation than bupivacaine. Some of these results were also affirmed in dorsal root ganglia neurons of C57 mice. The differences in the superoxidation and peroxidation induced by these agents suggest that different types of LAs may cause neurotoxicity via different pathways. We can target more accurate treatment based on their different mechanisms of neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine

Zhao

et al. 2017

Sci Rep

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“…15, 19, 35, 36 When administered intra-articulary, LA volumes can range from 12.5% to 50% of the total synovial capsule’s capacity, resulting in concentrations of 4-17 mM for lidocaine from a 1% (10 mg/mL) stock solution and 2-7 mM for bupivacaine from a 0.5% (5 mg/mL) stock solution. 2, 37 Although the concentrations used in this study are lower than clinically relevant concentrations, it is clear from our studies that exposure of macrophages and MSCs to anesthetics has a significant effect on their secretion and immunomodulatory function respectively.…”

Section: Discussionmentioning

confidence: 99%

The effect of local anesthetic on pro-inflammatory macrophage modulation by mesenchymal stromal cells

Gray

Marrero-Berríos

Weinberg

et al. 2016

International Immunopharmacology

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Administering local anesthetics (LAs) peri- and post-operatively aims to prevent or mitigate pain in surgical procedures and after tissue injury in cases of osteoarthritis (OA) and other degenerative diseases. Innovative tissue protective and reparative therapeutic interventions such as mesenchymal stromal cells (MSCs) are likely to be exposed to co-administered drugs such as LAs. Therefore, it is important to determine how this exposure affects the therapeutic functions of MSCs and other cells in their target microenvironment. In these studies, we measured the effect of LAs, lidocaine and bupivacaine, on macrophage viability and pro-inflammatory secretion. We also examined their effect on modulation of the macrophage pro-inflammatory phenotype in an in vitro co-culture system with MSCs, by quantifying macrophage tumor necrosis factor (TNF)-α secretion and MSC prostaglandin E2 (PGE2) production. Our studies indicate that both LAs directly attenuated macrophage TNF-α secretion, without significantly affecting viability, in a concentration- and potency-dependent manner. LA-mediated attenuation of macrophage TNF-α was sustained in co-culture with MSCs, but MSCs did not further enhance this anti-inflammatory effect. Concentration- and potency-dependent reductions in macrophage TNF-α were concurrent with decreased PGE2 levels in the co-cultures further indicating MSC-independent macrophage attenuation. MSC functional recovery from LA exposure was assessed by pre-treating MSCs with LAs prior to co-culture with macrophages. Both MSC attenuation of TNF-α and PGE2 secretion were impaired by pre-exposure to the more potent bupivacaine and high dose of lidocaine in a concentration-dependent manner. Therefore, LAs can affect anti-inflammatory function by both directly attenuating macrophage inflammation and MSC secretion and possibly by altering the local microenvironment which can secondarily reduce MSC function. Furthermore, the LA effect on MSC function may persist even after LA removal.

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Inflammatory signal transduction pathways induced by prilocaine toxicity in cultured ARPE‐19 cells

Öztüzün

Çeker

Yılmaz

et al. 2023

J Biochem & Molecular Tox

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Prilocaine (PRL) is a common local anesthetic. Despite the successful use of regional anesthesia for intraocular surgery, there are associated side effects that may affect the retina in case of accidental intravitreal injection. This study examined the signal transduction pathways activated by PRL toxicity and determined the protective role of nitric oxide synthase‐2 (NOS2) inhibition in cultured human‐derived retinal pigment epithelial cells (ARPE‐19). Toxicity analysis was performed using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide assay to detect the toxic dose of PRL and protective effectiveness of asperglaucide (ASP), an NOS2 inhibitor. Nuclear factor kappa B p65 (NF‐κB p65), phosphorylated NF‐κB p65, phospho‐protein kinase B (AKT), NOS2, nitrotyrosine, and cleaved caspase‐3 protein levels were evaluated by immunofluorescence staining and/or western blot analysis. Interleukin‐6 (IL‐6) and nitrated protein levels were quantified using an immunoassay, whereas caspase‐3 activity and nitrite/nitrate levels were measured using a fluorometric method. A significant increase in NF‐κB p65, and phosphorylated NF‐κB p65 and AKT levels due to PRL toxicity was observed. Similarly, IL‐6, NOS2, nitrite/nitrate, and nitrotyrosine levels were significantly higher in PRL‐treated cells than in control cells. Application of ASP to PRL‐treated cells reduced NF‐κB p65, and phosphorylated NF‐κB p65 and AKT to basal levels. IL‐6, NOS2, nitrite/nitrate, and nitrotyrosine levels also considerably decreased following ASP treatment in cells experiencing PRL‐induced toxicity. Moreover, the caspase‐3‐dependent apoptotic pathway was not activated. Our results indicate that ASP could ameliorate PRL‐induced activation of NF‐κB p65 that led to inflammation in cultured ARPE‐19 cells.

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The Comparative Cytotoxic Effects of Different Local Anesthetics on a Human Neuroblastoma Cell Line

Cited by 59 publications

References 40 publications

Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine

Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine

The effect of local anesthetic on pro-inflammatory macrophage modulation by mesenchymal stromal cells

Inflammatory signal transduction pathways induced by prilocaine toxicity in cultured ARPE‐19 cells

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