ArticleRedox biology2018
ROS-mediated lysosomal membrane permeabilization is involved in bupivacaine-induced death of rabbit intervertebral disc cells.
Article in Redox biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 85 citations in OpenAlex.
- Neoliensinine promotes lysosomal cell death in T cell malignancies via a novel STING-TUBA1B pathway.Genes & diseases · 2026Article
- Lysosomal Dysfunction Is Associated With Intervertebral Disc Degeneration: Multiomics and Machine Learning Identify Molecular Subtypes and Hub Genes.The journal of gene medicine · 2026Article
- ACSL4-Dependent Lysosomal Lipid Peroxidation Links WTAP-Mediated mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Preliminary Assessment of Anticancer Activity of Aqueous Meadowsweet (Biomedicines · 2026Article
- Cytoprotective Effects of Lipid Emulsion Against Bupivacaine-Induced Cytotoxicity in Human Rotator Cuff Fibroblasts.Antioxidants (Basel, Switzerland) · 2026Article
- Peroxynitrite regulates ER stress-mediated CaJournal of translational medicine · 2025Article
- Article
- Impaired RelA signaling and lipid metabolism dysregulation in hepatocytes: driving forces in the progression of metabolic dysfunction-associated steatotic liver disease.Cell death discovery · 2025Article
- Anticancer Activity of Benzo[Cells · 2024Article
- Investigation of the Protective Effects of Magnesium on Bupivacaine-Induced Toxicity at the Level of Colon Cell Culture.Biomedicines · 2024Article
- Lysosomal dysfunction and overload of nucleosides in thymidine phosphorylase deficiency of MNGIE.Journal of translational medicine · 2024Article
- The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization.PLoS pathogens · 2024Article
- Radiotherapy-activated NBTXR3 nanoparticles promote ferroptosis through induction of lysosomal membrane permeabilization.Journal of experimental & clinical cancer research : CR · 2024Article
- Light controlled self-escape capability of non-cationic carbon nitride-based nanosheets in lysosomes for hepatocellular carcinoma targeting stimulus-responsive gene delivery.Bioengineering & translational medicine · 2023Article
- Investigation of Molecular Mechanisms Involved in Sensitivity to the Anti-Cancer Activity of Costunolide in Breast Cancer Cells.International journal of molecular sciences · 2023Article
- ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models.Journal of inflammation research · 2023Article
- Cytotoxicity of Local Anesthetics on Bone, Joint, and Muscle Tissues: A Narrative Review of the Current Literature.Journal of pain research · 2023Review
- Catalase-deficient mice induce aging faster through lysosomal dysfunction.Cell communication and signaling : CCS · 2022Article
- Regulated cell death: Implications for intervertebral disc degeneration and therapy.Journal of orthopaedic translation · 2022Review
- Inhibition of PLA2G4E/cPLA2 promotes survival of random skin flaps by alleviating Lysosomal membrane permeabilization-Induced necroptosis.Autophagy · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bupivacaine is frequently administered for diagnosing and controlling spine-related pain in interventional spine procedures. However, the potential cytotoxic effects of bupivacaine on intervertebral disc (IVD) cells and the underlying molecular mechanisms have not yet been fully established. Here, we showed that bupivacaine decreased the viability of rabbit IVD cells in a dose- and time-dependent manner. Moreover, the short-term cytotoxicity of bupivacaine in IVD cells was primarily due to cell necrosis, as assessed by Annexin V-propidium iodide staining and live/dead cell staining. Necrosis was verified by observations of swollen organelles, plasma membrane rupture, and cellular lysis under transmission electronic microscopy. Interestingly, our data indicated that bupivacaine-induced primary necrosis might involve the necroptosis pathway. The key finding of this study was that bupivacaine was able to induce lysosomal membrane permeabilization (LMP) with the release of cathepsins into the cytosol, as evidenced by LysoTracker Red staining, acridine orange staining, and cathepsin D immunofluorescence staining. Consistently, inhibitors of lysosomal cathepsins, CA074-Me and pepstatin A, significantly reduced bupivacaine-induced cell death. Finally, we found that bupivacaine resulted in an increase in intracellular reactive oxygen species (ROS) and that inhibition of ROS by N-acetyl-L-cysteine effectively blocked bupivacaine-induced LMP and cell death. In summary, the results of this in vitro study reveal a novel mechanism underlying bupivacaine-induced cell death involving ROS-mediated LMP. Our findings establish a basis for the further investigation of bupivacaine cytotoxicity in an in vivo system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.