Analyze Diet
Veterinary anaesthesia and analgesia2011; 38(2); 127-133; doi: 10.1111/j.1467-2995.2010.00590.x

Comparison of the cytotoxic effects of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes.

Abstract: To compare the chondrotoxicity of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes in vitro. Methods: Prospective, experimental study. Methods: Equine articular chondrocytes. Methods: Primary cultured equine chondrocytes were exposed to 0.5% bupivacaine, 2% lidocaine, or 2% mepivacaine for 30 or 60 minutes. After treatment, cell viability was evaluated by trypan blue exclusion and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay in a dose dependent manner. Apoptosis and necrosis of chondrocytes were analyzed with the double staining of Hoechst 33258 and propidium iodide using fluorescence microscopy, and the results were confirmed using flow cytometry. Results: After 30-minute exposure, trypan blue exclusion assay revealed that cell viability of 0.5% bupivacaine group was 28.73±8.44%, and those of 2% lidocaine and 2% mepivacaine were 66.85±6.03% and 86.27±2.00%, respectively. The viability of chondrocytes after saline treatment was 95.95±2.75%. The results of MTT assay and fluorescence microscopy had similar tendency with trypan blue assay. Each result showed that bupivacaine was the most toxic of the three local anaesthetics. Mepivacaine was less toxic than lidocaine. The results of the viability test suggest that bupivacaine and lidocaine exhibit a marked chondrotoxicity, and that this is mainly due to necrosis rather than apoptosis. Conclusions: Bupivacaine may induce detrimental chondrotoxicity when administered intra-articularly, especially in patients with joint disease, and we suggest that it should be used cautiously in equine practice. Mepivacaine may be an alternative to both bupivacaine and lidocaine.
Publication Date: 2011-02-10 PubMed ID: 21303444DOI: 10.1111/j.1467-2995.2010.00590.xGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Comparative Study
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research compares the effects of three local anesthetics – bupivacaine, lidocaine, and mepivacaine – on horse joint cells, suggesting that bupivacaine is the most harmful, while mepivacaine is the least.

Methodology

  • The study was carried out with equine articular chondrocytes, which are cells present in horse joint cartilage.
  • The cells were cultured in primary conditions and then exposed to different concentrations of the three anesthetics (0.5% bupivacaine, 2% lidocaine, or 2% mepivacaine) for either 30 or 60 minutes.
  • Cell viability was measured after treatment gradually with two procedures: trypan blue exclusion – a method commonly used to determine the number of viable cells present in a cell suspension, and a biochemical test using a compound known as MTT.
  • The researchers also studied apoptosis (controlled cell death) and necrosis (uncontrolled cell death often due to injury or disease) using special stains and checking under a fluorescence microscope. This was further confirmed with flow cytometry – a technique used to measure the physical and chemical characteristics of cells.

Findings

  • The cell viability measured using trypan blue assay showed that 0.5% bupivacaine was the most lethal with around 29% of the cells surviving, while lidocaine and mepivacaine registered around 67% and 86% survival rates, respectively.
  • Cell survival rate was nearly 96% after saline treatment, showing the toxic effect of the anesthetics.
  • Similar patterns were observed in the MTT test and during microscopic examination.
  • On analyzing the cause of cell death, it was found that necrosis, not apoptosis, was primarily behind chondrotoxicity.

Conclusion

  • Of the three anesthetics tested, bupivacaine was found to have the most significant chondrotoxicity effect on equine chondrocytes. Lidocaine also exhibited notable levels of chondrotoxicity.
  • Mepivacaine caused less harm to the cells, thus could be a safer alternative to the other two anesthetics.
  • The researchers advised cautious use of bupivacaine, especially in horses with joint conditions.

Cite This Article

APA
Park J, Sutradhar BC, Hong G, Choi SH, Kim G. (2011). Comparison of the cytotoxic effects of bupivacaine, lidocaine, and mepivacaine in equine articular chondrocytes. Vet Anaesth Analg, 38(2), 127-133. https://doi.org/10.1111/j.1467-2995.2010.00590.x

Publication

ISSN: 1467-2995
NlmUniqueID: 100956422
Country: United States
Language: English
Volume: 38
Issue: 2
Pages: 127-133

Researcher Affiliations

Park, Jinuk
  • Laboratory of Veterinary Surgery, College of Veterinary Medicine, Chungbuk National University, Cheongju, Korea.
Sutradhar, Bibek C
    Hong, Gyeongmi
      Choi, Seok H
        Kim, Gonhyung

          MeSH Terms

          • Anesthetics, Local / pharmacology
          • Animals
          • Bupivacaine / pharmacology
          • Cartilage, Articular / drug effects
          • Cell Survival / drug effects
          • Cells, Cultured
          • Chondrocytes / drug effects
          • Flow Cytometry / veterinary
          • Horses
          • Lidocaine / pharmacology
          • Mepivacaine / pharmacology
          • Microscopy, Fluorescence / veterinary

          Citations

          This article has been cited 26 times.
          1. Zhang K, Li M, Yao W, Wan L. Cytotoxicity of Local Anesthetics on Bone, Joint, and Muscle Tissues: A Narrative Review of the Current Literature. J Pain Res 2023;16:611-621.
            doi: 10.2147/JPR.S398329pubmed: 36875687google scholar: lookup
          2. Adler DMT, Jørgensen E, Cornett C. The concentration of lidocaine and mepivacaine measured in synovial fluid of different joints of horses after single intra-articular injection. Front Vet Sci 2022;9:1007399.
            doi: 10.3389/fvets.2022.1007399pubmed: 36439347google scholar: lookup
          3. Wang W, Xiao B, Yu L, Wang H, Qi J, Xi Y, Deng G, Gu X, Xu G. Effect of species, concentration and volume of local anesthetics on intervertebral disk degeneration in rats with discoblock. Eur Spine J 2022 Nov;31(11):2960-2971.
            doi: 10.1007/s00586-022-07398-2pubmed: 36152221google scholar: lookup
          4. Hussein K, Abdelbaset AE, Sadek AA, Noreldin A. In vitro and in vivo Effects of a Single Dose of Bupivacaine 5% on Donkey Chondrocytes. Front Vet Sci 2021;8:661426.
            doi: 10.3389/fvets.2021.661426pubmed: 34888370google scholar: lookup
          5. Vaiciuleviciute R, Bironaite D, Uzieliene I, Mobasheri A, Bernotiene E. Cardiovascular Drugs and Osteoarthritis: Effects of Targeting Ion Channels. Cells 2021 Sep 28;10(10).
            doi: 10.3390/cells10102572pubmed: 34685552google scholar: lookup
          6. Imran E, Moeen F, Abbas B, Yaqoob B, Wajahat M, Khan Q, Khurshid Z. Comparative Analysis of Different Local Anesthetic Solutions Available in Market: An In Vitro and Clinical Study. Eur J Dent 2021 Oct;15(4):660-668.
            doi: 10.1055/s-0041-1727553pubmed: 34041728google scholar: lookup
          7. Kohli S, Tandra V, Gulihar A. Effect of various factors on articular cartilage and their implications on arthroscopic procedures: A review of literature. J Clin Orthop Trauma 2020 May;11(Suppl 3):S396-S401.
            doi: 10.1016/j.jcot.2019.06.017pubmed: 32523300google scholar: lookup
          8. Liu CT, Yang TF. Intra-substance steroid injection for full-thickness supraspinatus tendon rupture. BMC Musculoskelet Disord 2019 Nov 27;20(1):569.
            doi: 10.1186/s12891-019-2952-ypubmed: 31775808google scholar: lookup
          9. Hurley P, Alnajjar F, Wijesinghe S, Nanus DE, Davis ET, Jones SW. The combination of local infiltration analgesia reagents increases their detrimental effect on human hip OA patient osteoblast viability and function. J Orthop 2019 Sep-Oct;16(5):434-439.
            doi: 10.1016/j.jor.2019.06.014pubmed: 31516213google scholar: lookup
          10. Di Salvo A, Chiaradia E, Della Rocca G, Giorgi M, Mancini F, Marenzoni ML, Conti MB, Nannarone S. Efficacy, chondrotoxicity and plasma concentrations of tramadol following intra-articular administration in horses undergoing arthroscopy: preliminary findings. Vet Q 2018 Dec;38(1):129-137.
            doi: 10.1080/01652176.2018.1546963pubmed: 30773122google scholar: lookup
          11. Bianchini E, Mancini F, Di Meo A, Stabile A, Buratta S, Moscati L, Pistilli A, Floridi C, Pepe M, Chiaradia E. Protective effects of platelet-rich plasma against lidocaine cytotoxicity on canine articular chondrocytes. Acta Vet Scand 2018 Oct 26;60(1):63.
            doi: 10.1186/s13028-018-0418-0pubmed: 30367652google scholar: lookup
          12. Rubio-Martínez LM, Rioja E, Castro Martins M, Wipawee S, Clegg P, Peffers MJ. Local anaesthetics or their combination with morphine and/or magnesium sulphate are toxic for equine chondrocytes and synoviocytes in vitro. BMC Vet Res 2017 Nov 7;13(1):318.
            doi: 10.1186/s12917-017-1244-8pubmed: 29115971google scholar: lookup
          13. Yu XJ, Zhao W, Li YJ, Li FX, Liu ZJ, Xu HL, Lai LY, Xu R, Xu SY. Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine. Sci Rep 2017 Mar 24;7:45316.
            doi: 10.1038/srep45316pubmed: 28338089google scholar: lookup
          14. Kreuz PC, Steinwachs M, Angele P. Single-dose local anesthetics exhibit a type-, dose-, and time-dependent chondrotoxic effect on chondrocytes and cartilage: a systematic review of the current literature. Knee Surg Sports Traumatol Arthrosc 2018 Mar;26(3):819-830.
            doi: 10.1007/s00167-017-4470-5pubmed: 28289821google scholar: lookup
          15. Bentov I, Damodarasamy M, Spiekerman C, Reed MJ. Lidocaine Impairs Proliferative and Biosynthetic Functions of Aged Human Dermal Fibroblasts. Anesth Analg 2016 Sep;123(3):616-23.
            doi: 10.1213/ANE.0000000000001422pubmed: 27537755google scholar: lookup
          16. Gulihar A, Robati S, Twaij H, Salih A, Taylor GJ. Articular cartilage and local anaesthetic: A systematic review of the current literature. J Orthop 2015 Dec;12(Suppl 2):S200-10.
            doi: 10.1016/j.jor.2015.10.005pubmed: 27047224google scholar: lookup
          17. Yang Y, Zeng C, Wei J, Li H, Yang T, Deng ZH, Li YS, Yang TB, Lei GH. Single-dose intra-articular bupivacaine plus morphine versus bupivacaine alone after arthroscopic knee surgery: a meta-analysis of randomized controlled trials. Knee Surg Sports Traumatol Arthrosc 2017 Mar;25(3):966-979.
            doi: 10.1007/s00167-015-3748-8pubmed: 26264382google scholar: lookup
          18. Olstad K, Hendrickson EH, Ekman S, Carlson CS, Dolvik NI. Local Morphological Response of the Distal Femoral Articular-Epiphyseal Cartilage Complex of Young Foals to Surgical Stab Incision and Potential Relevance to Cartilage Injury and Repair in Children. Cartilage 2013 Jul;4(3):239-48.
            doi: 10.1177/1947603513480024pubmed: 26069670google scholar: lookup
          19. Zhou Y, Yang TB, Wei J, Zeng C, Li H, Yang T, Lei GH. Single-dose intra-articular ropivacaine after arthroscopic knee surgery decreases post-operative pain without increasing side effects: a systematic review and meta-analysis. Knee Surg Sports Traumatol Arthrosc 2016 May;24(5):1651-9.
            doi: 10.1007/s00167-015-3656-ypubmed: 26049805google scholar: lookup
          20. Dregalla RC, Lyons NF, Reischling PD, Centeno CJ. Amide-type local anesthetics and human mesenchymal stem cells: clinical implications for stem cell therapy. Stem Cells Transl Med 2014 Mar;3(3):365-74.
            doi: 10.5966/sctm.2013-0058pubmed: 24436443google scholar: lookup
          21. Wei J, Yang HB, Qin JB, Kong FJ, Yang TB. Single-dose intra-articular bupivacaine after knee arthroscopic surgery: a meta-analysis of randomized placebo-controlled studies. Knee Surg Sports Traumatol Arthrosc 2014 Jul;22(7):1517-28.
            doi: 10.1007/s00167-013-2543-7pubmed: 23749215google scholar: lookup
          22. Mobasheri A, Lewis R, Ferreira-Mendes A, Rufino A, Dart C, Barrett-Jolley R. Potassium channels in articular chondrocytes. Channels (Austin) 2012 Nov-Dec;6(6):416-25.
            doi: 10.4161/chan.22340pubmed: 23064164google scholar: lookup
          23. Braun HJ, Busfield BT, Kim HJ, Scuderi GJ, Dragoo JL. The effect of local anaesthetics on synoviocytes: a possible indirect mechanism of chondrolysis. Knee Surg Sports Traumatol Arthrosc 2013 Jun;21(6):1468-74.
            doi: 10.1007/s00167-012-2104-5pubmed: 22717739google scholar: lookup
          24. Baker JF, Mulhall KJ. Local anaesthetics and chondrotoxicty: What is the evidence?. Knee Surg Sports Traumatol Arthrosc 2012 Nov;20(11):2294-301.
            doi: 10.1007/s00167-011-1804-6pubmed: 22134409google scholar: lookup
          25. Arias-Vázquez PI, Ramírez-Wakamatzu MA, Legorreta-Ramírez BG. Biopuncture, A Multitarget Therapy in the Treatment of Individuals with Knee Osteoarthritis: state of the art. J Pharmacopuncture 2024 Sep 30;27(3):190-198.
            doi: 10.3831/KPI.2024.27.3.190pubmed: 39350927google scholar: lookup
          26. Dimopoulou I, Anagnostou T, Savvas I, Karamichali P, Prassinos N. Comparison between the Effect of Lidocaine or Ropivacaine Hematoma Block and of Different Timings of Administration on Post-Operative Pain in Dogs Undergoing Osteosynthesis of Long-Bone Fractures. Animals (Basel) 2023 Sep 8;13(18).
            doi: 10.3390/ani13182858pubmed: 37760258google scholar: lookup