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Immunomodulatory effectiveness of licofelone in preventing epidural fibrosis in post-laminectomy rat

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European Journal of Orthopaedic Surgery & Traumatology Aims and scope Submit manuscript

Abstract

Objective

The object of this study was to investigate the effects of licofelone on the prevention of epidural fibrosis (EF) formation in post-laminectomy rat models.

Methods

A controlled double-blinded study was conducted in sixty, healthy adult Wistar rats that underwent laminectomy at the L1–L2 vertebrae levels. All the rats were divided randomly into three groups according to the treatment (via oral gavage): (1) licofelone treatment group; (2) vehicle treatment group; (3) sham group (laminectomy without treatment). All rats were euthanized humanely 4 weeks postoperatively. The macroscopic assessment of EF, hydroxyproline content in epidural scar tissue, histological analysis, and the mRNA measurements of interleukin-6 (IL-6) and transforming growth factor-β1 were performed.

Results

The Rydell score, hydroxyproline content, epidural scar density, and inflammatory factors expressions all suggested better results in licofelone group than the other two groups.

Conclusion

The application of licofelone could reduce hydroxyproline deposits, inflammatory factors expressions and prevent epidural adhesions in post-laminectomy rats.

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References

  1. Guyer RD, Patterson M, Ohnmeiss DD (2006) Failed back surgery syndrome: diagnostic evaluation. J Am Acad Orthop Surg 14(9):534–543

    PubMed  Google Scholar 

  2. Ross JS, Robertson JT, Frederickson RC, Petrie JL, Obuchowski N, Modic MT, deTribolet N (1996) Association between peridural scar and recurrent radicular pain after lumbar discectomy: magnetic resonance evaluation. Neurosurgery 38:855–861

    Article  CAS  PubMed  Google Scholar 

  3. Cauchoix J, Ficat J, Girard B (1978) Repeat surgery after disc excision. Spine 3:256–259

    Article  CAS  PubMed  Google Scholar 

  4. Key JA, Ford LT (1948) Experimental intervertebral disc-lesions. J Bone Joint Surg Am 30:621–630

    Google Scholar 

  5. Ceviz A, Arslan A, Ak HE, Inalöz S (1997) The effect of urokinase in preventing the formation of epidural fibrosis and/or leptomeningeal arachnoiditis. Surg Neurol 47:124–127

    Article  CAS  PubMed  Google Scholar 

  6. Cruccu G, Aziz TZ, Garcia-Larrea L, Hansson P, Jensen TS, Lefaucheur JP, Simpson BA, Taylor RS (2007) EFNS guidelines on neurostimulation therapy for neuropathic pain. Eur J Neurol 14:952–970

    Article  CAS  PubMed  Google Scholar 

  7. Gill GG, Scheck M, Kelley ET, Rodrigo JJ (1985) Pedicle fat grafts for the prevention of scar in low back surgery. A preliminary report on the first 92 cases. Spine 10:662–667

    Article  CAS  PubMed  Google Scholar 

  8. Sandoval MA, Hernandez-Vaquero D (2008) Preventing peridural fibrosis with nonsteroidal anti-inflammatory drugs. Eur Spine J 17:451–455

    Article  PubMed Central  PubMed  Google Scholar 

  9. Xu J, Chen Y, Yue Y, Sun J, Cui L (2012) Reconstruction of epidural fat with engineered adipose tissue from adipose derived stem cells and PLGA in the rabbit dorsal laminectomy model. Biomaterials 33:6965–6973

    Article  CAS  PubMed  Google Scholar 

  10. Lee HM, Yang KH, Han DY, Kim NH (1990) An experimental study on prevention of postlaminectomy scar formation. Yonsei Med J 31:359–366

    Article  CAS  PubMed  Google Scholar 

  11. Barberá J, Gonzalez J, Esquerdo J, Broseta J, Barcia-Salorio JL (1978) Prophylaxis of the laminectomy membrane. An experimental study in dogs. J Neurosurg 49:419–424

    Article  PubMed  Google Scholar 

  12. Bartzatt R (2012) Anti-inflammatory drugs and prediction of new structures by comparative analysis. Anti-Inflamm Anti-Allergy Agents Med Chem 11:151–160

    Article  CAS  Google Scholar 

  13. Liu W, Zhou J, Liu Y, Liu H, Bensdorf K, Guo C, Gust R (2011) Licofelone-nitric oxide donors as anticancer agents. Arch Pharm (Weinheim) 344:487–493

    Article  CAS  Google Scholar 

  14. Kabadere S, Kus G, Uyar R, Oztopcu-Vatan P (2013) Licofelone abolishes survival of carcinogenic fibroblasts by inducing apoptosis. Drug Chem Toxicol [Epub ahead of print]

  15. Dulin JN, Karoly ED, Wang Y, Strobel HW, Grill RJ (2013) Licofelone modulates neuroinflammation and attenuates mechanical hypersensitivity in the chronic phase of spinal cord injury. J Neurosci 33:652–664

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Rydell N (1970) Decreased granulation tissue reaction after installment of hyaluronic acid. Acta Orthop Scand 41:307–311

    Article  CAS  PubMed  Google Scholar 

  17. Zhang C, Kong X, Liu C, Liang Z, Zhao H, Tong W, Ning G, Shen W, Yao L, Feng S (2014) ERK2 small interfering RNAs prevent epidural fibrosis via the efficient inhibition of collagen expression and inflammation in laminectomy rats. Biochem Biophys Res Commun 444:395–400

    Article  CAS  PubMed  Google Scholar 

  18. Zhang C, Kong X, Zhou H, Liu C, Zhao X, Zhou X, Su Y, Sharma HS, Feng S (2013) An experimental novel study: Angelica sinensis prevents epidural fibrosis in laminectomy rats via downregulation of hydroxyproline, IL-6, and TGF-β1. Evid Based Complement Altern Med. doi:10.1155/2013/291814

    Google Scholar 

  19. Zhang C, Kong X, Ning G, Liang Z, Qu T, Chen F, Cao D, Wang T, Sharma HS, Feng S (2014) All-trans retinoic acid prevents epidural fibrosis through NF-κB signaling pathway in post-laminectomy rats. Neuropharmacology 79:275–281

    Article  CAS  PubMed  Google Scholar 

  20. Yang J, Ni B, Liu J, Zhu L, Zhou W (2011) Application of liposome-encapsulated hydroxycamptothecin in the prevention of epidural scar formation in New Zealand white rabbits. Spine J 11:218–223

    Article  PubMed  Google Scholar 

  21. MacKay MA, Fischgrund JS, Herkowitz HN, Kurz LT, Hecht B, Schwartz M (1995) The effect of interposition membrane on the outcome of lumbar laminectomy and discectomy. Spine (Phila Pa 1976) 20:1793–1796

  22. Jou IM, Tai TW, Tsai CL, Tsai TM, Yung WS, Jung YC (2007) Spinal somatosensory evoked potential to evaluate neurophysiologic changes associated with postlaminotomy fibrosis: an experimental study. Spine (Phila Pa 1976) 32:2111–2118

  23. Dulin JN, Moore ML, Grill RJ (2013) The dual cyclooxygenase/5-lipoxygenase inhibitor licofelone attenuates p-glycoprotein-mediated drug resistance in the injured spinal cord. J Neurotrauma 30:211–226

    Article  PubMed Central  PubMed  Google Scholar 

  24. Kulkarni SK, Singh VP (2008) Licofelone: the answer to unmet needs in osteoarthritis therapy? Curr Rheumatol Rep 10:43–48

    Article  CAS  PubMed  Google Scholar 

  25. Tavolari S, Bonafè M, Marini M, Ferreri C, Bartolini G, Brighenti E, Manara S, Tomasi V, Laufer S, Guarnieri T (2008) Licofelone, a dual COX/5-LOX inhibitor, induces apoptosis in HCA-7 colon cancer cells through the mitochondrial pathway independently from its ability to affect the arachidonic acid cascade. Carcinogenesis 29:371–380

    Article  CAS  PubMed  Google Scholar 

  26. Hamby ME, Hewett JA, Hewett SJ (2008) TGF-beta1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner. Prostaglandins Other Lipid Mediat 85:115–124

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Luo J, Lang JA, Miller MW (1998) Transforming growth factor beta1 regulates the expression of cyclooxygenase in cultured cortical astrocytes and neurons. J Neurochem 71:526–534

    Article  CAS  PubMed  Google Scholar 

  28. Wu YJ, Xue M, Chen H (2012) Licofelone inhibits interleukin-18-induced pro-inflammatory cytokine release and cellular proliferation in human mesangial cells. Basic Clin Pharmacol Toxicol 111:166–172

    CAS  PubMed  Google Scholar 

  29. Sung JY, Park SY, Kim JH, Kang HG, Yoon JH, Na YS, Kim YN, Park BK (2014) Interferon consensus sequence-binding protein (ICSBP) promotes epithelial-to-mesenchymal transition (EMT)-like phenomena, cell-motility, and invasion via TGF-β signaling in U2OS cells. Cell Death Dis. doi:10.1038/cddis.2014.189

    PubMed Central  PubMed  Google Scholar 

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Correspondence to Jinmin Zhao.

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Zhang, K., Zhao, J., Su, W. et al. Immunomodulatory effectiveness of licofelone in preventing epidural fibrosis in post-laminectomy rat. Eur J Orthop Surg Traumatol 25 (Suppl 1), 63–68 (2015). https://doi.org/10.1007/s00590-014-1534-9

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  • DOI: https://doi.org/10.1007/s00590-014-1534-9

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