Melatonin ameliorates bupivacaine-induced spinal neurotoxicity in rats by suppressing neuronal NLRP3 inflammasome activation

Lai, Jian; Ji, Jiemei; Chen, Mei-yun-zi; Luo, Yunpeng; Yu, Yue; Zhou, Gang; Wei, Liling; Huang, Lanshan; Liu, Jingchen

doi:10.1016/j.neulet.2022.136472

Cited by 6 publications

(6 citation statements)

References 19 publications

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“…Intrathecal catheterization was done as previously described [ 11 ]. Before surgery, animals were anesthetized using 1% pentobarbital sodium (50 mg/kg, i.p.).…”

Section: Methodsmentioning

confidence: 99%

“…Lumbar enlargement spinal cord tissues were collected for western blot analysis as previously described [ 11 ]. After protein transfer, membranes were incubated overnight (4°C) with primary antibodies against PERK (1 : 1000, CST), ATF4 (1 : 1000, CST), CHOP (1 : 1000, CST), p-eIF2 α (1 : 1000, Abcam), eIF2 α (1 : 1000, Abcam), Caspase12 (1 : 1000, Abcam), p-PERK (1 : 1000, Wanleibio), Bcl2 (1 : 1000, Wanleibio), cleaved Caspase3 (1 : 1000, Proteintech), GRP78 (1 : 1000; Proteintech), Bax (1 : 1000, Proteintech), and GAPDH (1 : 10000, Proteintech).…”

Section: Methodsmentioning

confidence: 99%

“…Western Blot. Lumbar enlargement spinal cord tissues were collected for western blot analysis as previously described [11]. After protein transfer, membranes were incubated overnight (4…”

Section: Rt-pcr Analysismentioning

confidence: 99%

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[Retracted] Resveratrol Suppresses Bupivacaine‐Induced Spinal Neurotoxicity in Rats by Inhibiting Endoplasmic Reticulum Stress via SIRT1 Modulation

Luo

Zhao

Lai

et al. 2023

BioMed Research International

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Bupivacaine (BUP) may cause neurotoxic effects after spinal anesthesia. Resveratrol (RSV), a natural agonist of Silent information regulator 1 (SIRT1), protects various tissues and organs from damage by regulating endoplasmic reticulum (ER) stress. The aim of this study is to explore whether RSV could alleviate the neurotoxicity induced by bupivacaine via regulating ER stress. We established a model of bupivacaine-induced spinal neurotoxicity in rats using intrathecal injection of 5% bupivacaine. The protective effect of RSV was evaluated by injecting intrathecally with 30 μg/μL RSV in total of 10 μL per day for 4 consecutive days. On day 3 after bupivacaine administration, tail-flick latency (TFL) tests and the Basso, Beattie, and Bresnahan (BBB) locomotor scores were assessed to neurological function, and the lumbar enlargement of the spinal cord was obtained. H&E and Nissl staining were used to evaluate the histomorphological changes and the number of survival neurons. TUNEL staining was conducted to determine apoptotic cells. The expression of proteins was detected by IHC, immunofluorescence, and western blot. The mRNA level of SIRT1 was determined by RT-PCR. Bupivacaine caused spinal cord neurotoxicity by inducing cell apoptosis and triggering ER stress. RSV treatment promoted the recovery of neurological dysfunction after bupivacaine administration by suppressing neuronal apoptosis and ER stress. Furthermore, RSV upregulated SIRT1 expression and inhibited PERK signaling pathway activation. In summary, resveratrol suppresses bupivacaine-induced spinal neurotoxicity in rats by inhibiting endoplasmic reticulum stress via SIRT1 modulation.

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“…Intrathecal catheterization was done as previously described [ 11 ]. Before surgery, animals were anesthetized using 1% pentobarbital sodium (50 mg/kg, i.p.).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

[Retracted] Resveratrol Suppresses Bupivacaine‐Induced Spinal Neurotoxicity in Rats by Inhibiting Endoplasmic Reticulum Stress via SIRT1 Modulation

Luo

Zhao

Lai

et al. 2023

BioMed Research International

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“… 33 Intriguingly, melatonin is capable of modulating neuronal inflammatory factors, and oxidative stress, thereby alleviating neurotoxicity. 34 , 35 However, there is limited evidence that melatonin ameliorates the neurotoxicity caused by ZnONPs in mammals. It is unclear whether oral administration of ZnONPs affects melatonin secretion, transport, and circadian rhythms in vivo.…”

Section: Discussionmentioning

confidence: 99%

Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles

Yang¹,

Lu²,

Xia³

et al. 2023

IJN

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Purpose The widespread use of zinc oxide nanoparticles (ZnONPs) has raised concerns about its potential toxicity. Melatonin is a neurohormone with tremendous anti-toxic effects. The enterochromaffin cells are an essential source of melatonin in vivo. However, studies on the effects of ZnONPs on endogenous melatonin are minimal. In the present study, we aimed to investigate the effects of ZnONPs exposure on gut-derived melatonin. Methods In the present study, 64 adult male mice were randomly and equally divided into four groups, and each group was exposed to ZnONPs (0, 6.5, 13, 26 mg/kg/day) for 30 days. Subsequently, the neurobehavioral changes were observed. The effects of ZnONPs on the expression of melatonin-related genes arylalkylamine N-acetyltransferase ( Aanat ), melatonin receptor1A ( Mt1 / Mtnr1a ), melatonin receptor1B ( Mt2 / Mtnr1b ), and neuropeptide Y ( Npy ) on melatonin synthesis and secretion in duodenum, jejunum, ileum and colon during day and night were also assessed. Results The results revealed that oral exposure to ZnONPs induced impairments of locomotor activity and anxiety-like behavior in adult mice during the day. The transcriptional analysis of brain tissues revealed that exposure to ZnONPs caused profound effects on genes and transcriptional signaling pathways associated with melatonin synthesis and metabolic processes during the day and night. We also observed that, in the duodenum, jejunum, ileum and colon sites, ZnONPs resulted in a significant reduction in the expression of the gut-derived melatonin rate-limiting enzyme Aanat , the membrane receptors Mt1 and Mt2 and Npy during the day and night. Conclusion Taken together, this is the first study shows that oral exposure to ZnONPs interferes with melatonin synthesis and secretion in different intestinal segments of adult mice. These findings will provide novelty insights into the neurotoxic mechanisms of ZnONPs and suggest an alternative strategy for the prevention of ZnONP neurotoxicity.

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“…Since the introduction of local anesthetics, they have been widely used in the clinic and have greatly promoted the rapid development of clinical anesthesia and surgery. However, numerous clinical research studies [ 1 , 2 ] and basic research studies [ 3 , 4 ] have shown that local anesthetics can cause nerve damage. The interspinal neurotoxicity of local anesthetics is mainly characterized by transient neurological syndrome (TNS), cauda equina syndrome (CES) and other poorly defined symptoms of neurotoxicity, including mental and behavioral abnormalities [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

P53 and taurine upregulated gene 1 promotes the repair of the DeoxyriboNucleic Acid damage induced by bupivacaine in murine primary sensory neurons

et al. 2022

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The research aimed to explore the biological role of p53 protein and long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) in bupivacaine (bup)-induced neurotoxicity. Our work treated dorsal root ganglion (DRG) cells with bup, detected cell viability through CCK-8, apoptosis through TUNEL assays, DeoxyriboNucleic Acid (DNA) damage through γ-H2AX protein and comet assay, including p53 mRNA, protein and TUG1 expression through q-PCR and western blot, furthermore, cell viability and DNA damage were determined after the silencing of p53 and TUG1, biological information and TUG1 FISH combined with p53 protein immunofluorescence (IF) was performed to determine the cellular localization of these molecule. In vivo experiments, we explored the impact of intrathecal injection of bup on p53 mRNA and protein, TUG1, γ-H2AX protein expression. The results showed that bup was available to signally decreased cell viability, promoted apoptosis rate and DNA damage, additionally, bup increased p53 mRNA and protein and TUG1 expression. P53 siRNA and TUG1 siRNA significantly increased DNA damage. Furthermore, bioinformatics analysis and colocalization experiments revealed that the p53 protein is a transcription factor of TUG1, in vivo experiment, intrathecal injection of bup increased the p53 mRNA, p53 protein, TUG1 and γ-H2AX protein in the murine DRG. In this study, it was found p53 and TUG1 promote the repair of the DNA damage induced by bup in murine dorsal root ganglion cells, suggesting a new strategy for the amelioration of bup-induced neurotoxicity.

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Melatonin ameliorates bupivacaine-induced spinal neurotoxicity in rats by suppressing neuronal NLRP3 inflammasome activation

Cited by 6 publications

References 19 publications

[Retracted] Resveratrol Suppresses Bupivacaine‐Induced Spinal Neurotoxicity in Rats by Inhibiting Endoplasmic Reticulum Stress via SIRT1 Modulation

[Retracted] Resveratrol Suppresses Bupivacaine‐Induced Spinal Neurotoxicity in Rats by Inhibiting Endoplasmic Reticulum Stress via SIRT1 Modulation

Alterations of Gut-Derived Melatonin in Neurobehavioral Impairments Caused by Zinc Oxide Nanoparticles

P53 and taurine upregulated gene 1 promotes the repair of the DeoxyriboNucleic Acid damage induced by bupivacaine in murine primary sensory neurons

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