Document Type : Research Paper

Authors

1 1. M.Sc student, Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran

2 Associate Professo, Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran

3 3. Associate Professo, Department of Engineering Sciences, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, Iran

4 Ph.D student, Department of Biology, Faculty of Science, University of Mohaghegh Ardabili, Ardabil, Iran

Abstract

Introduction: Improvement of peripheral nerve damage is one of the most important challenges clinically. Using new methods such as nano drugs and natural compounds can be a suitable option due to their effective effects and less side effects. In this study, the synergistic effects of eugenol and cerium oxide nanoparticles was investigated on sciatic nerve recovery in a rat model. Method and material: In this study, twenty-eight male rats weighing 250-300 g were divided into four groups (n=7). The control group and sciatica model injected saline (0.5ml, IP). Two groups model sciatic received intraperitoneally (50 mg/kg eugenol and 20 mg/kg cerium oxide nanoparticles) or (100 mg/kg eugenol and 20 mg/kg cerium oxide nanoparticles). Then sensory and motor behavioral tests performed. The muscle tissue removed. Finally, changes in muscle weight investigated. Results: Intraperitoneal injection of eugenol plus cerium oxide nanoparticles increased the recovery speed of sensory and motor neurons compared to the sciatica model group. Also, in the group receiving eugenol plus cerium oxide the amount of muscle atrophy was lower. The improvement of nerve tissue was significant in the high-dose group. Conclusion: The results showed that eugenol/cerium oxide accelerates the regeneration of nerve tissue. Therefore, its neuroprotective potential can be used to treat diseases related to peripheral nerve damage.

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Alminderej, F., Bakari, S., Almundarij, T. I., Snoussi, M., Aouadi, K. and  Kadri, A. (2020). Antioxidant activities of a new chemotype of Piper cubeba L. fruit essential oil (Methyleugenol/Eugenol). In Silico molecular docking and ADMET studies Plants, 9(11): 1534.
Alypoor, S., Abdolmaleki, A., Mamoudi, F., Haghighat, K., Soluki, M. (2023). Evaluation of the Neuroprotective Effect of Eugenol on the Improvement of Sciatic Nerve Injury in Rats. Iranian Journal of Toxicology, 17(3):53-59.
Azimpour, M., Mahmoudi, F., Abdolmaleki, A. and Bayrami, A. (2022). Thyroxine accelerates functional recovery in a rat model of sciatic nerve crush. Turk Neurosurg, 32(2): 298-304.
Babazadeh, A., Vahed, F. M., Liu, Q., Siddiqui, S. A., Kharazmi, M. S. and Jafari, S. M. (2023). Natural Bioactive Molecules as Neuromedicines for the Treatment/Prevention of Neurodegenerative Diseases. ACS omega, 8(4): 3667-3683.
Barot, J. and Saxena, B. (2021). Therapeutic effects of eugenol in a rat model of traumatic brain injury: A behavioral, biochemical, and histological study. Journal of Traditional and Complementary Medicine, 11(4): 318-327.‏
Beltrán-Gracia, E., López-Camacho, A., Higuera-Ciapara, I., Velázquez-Fernández, J. B. and Vallejo-Cardona, A. A. (2019). Nanomedicine review: Clinical developments in liposomal applications. Cancer Nanotechnology, 10(1): 1-40.
Choi, C. Y., Park, K. R., Lee, J. H., Jeon, Y. J., Liu, K. H., Oh, S. and Yea, S. S. (2007). Isoeugenol suppression of inducible nitric oxide synthase expression is mediated by down-regulation of NF-κB, ERK1/2, and p38 kinase. European journal of pharmacology, 576(1-3): 151-159.
Cui, Z., Liu, Z., Zeng, J., Chen, L., Wu, Q., Mo, J. and & Guo, X. (2019). Eugenol inhibits non‐small cell lung cancer by repressing expression of NF‐κB‐regulated TRIM59. Phytotherapy Research, 33(5): 1562-1569.
Davis, D., Maini, K., Vasudevan, A. (2022) Sciatica. In: StatPearls. StatPearls Publishing. Treasure Island (FL), 29939685.
de Araújo Lopes, A., da Fonseca, F. N., Rocha, T. M., de Freitas, L. B., Araújo, E. V. O., Wong, D. V. T., & Leal, L. K. A. M. (2018). Eugenol as a promising molecule for the treatment of dermatitis: antioxidant and anti-inflammatory activities and its nanoformulation. Oxidative medicine and cellular longevity.
Estevez, A. Y., Pritchard, S., Harper, K., Aston, J. W., Lynch, A., Lucky, J. J., Ludington, J.S., Chatani, P.,  Mosenthal, W.P., Leiter, J.C., Andreescu, S., Erlichman, J. S. (2011). Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia. Free Radical Biology and Medicine, 51(6): 1155-1163.
Fernandez, M., Hartvigsen, J., Ferreira, M. L., Refshauge, K. M., Machado, A. F., Lemes, Í. R. and Ferreira, P. H. (2015). Advice to stay active or structured exercise in the management of sciatica. Spine, 40(18): 1457-1466.‏
Hazer Rosberg, D. B., Hazer, B., Stenberg, L. and Dahlin, L. B. (2021). Gold and cobalt oxide nanoparticles modified poly-propylene poly-ethylene glycol membranes in poly (ε-Caprolactone) conduits enhance nerve regeneration in the sciatic nerve of healthy Rats. International Journal of Molecular Sciences, 22(13): 7146.‏
Hekmatimoghaddam, S., Iman, M., Sardo, H. S. and Jebali, A. (2019). Gelatin hydrogel containing cerium oxide nanoparticles covered by interleukin-17 aptamar as an anti-inflammatory agent for brain inflammation. Journal of neuroimmunology, 326: 79-83.‏
Huang, X., Liu, Y., Lu, Y. and Ma, C. (2015). Anti-inflammatory effects of eugenol on lipopolysaccharide-induced inflammatory reaction in acute lung injury via regulating inflammation and redox status. International immunopharmacology, 26(1): 265-271.
Irie, Y. (2006). Effects of eugenol on the central nervous system: its possible application to treatment of Alzheimer's disease, depression, and Parkinson's disease. Current Bioactive Compounds, 2(1): 57-66.
Jahromi, M., Razavi, S., Seyedebrahimi, R., Reisi, P. and Kazemi, M. (2021). Regeneration of rat sciatic nerve using PLGA conduit containing rat ADSCs with controlled release of BDNF and gold nanoparticles. Journal of Molecular Neuroscience, 71: 746-760.‏
Jensen, R. K., Kongsted, A., Kjaer, P. and Koes, B. (2019). Diagnosis and treatment of sciatica. bmj, 367.
Jungen, M. J., Ter Meulen, B. C., Van Osch, T., Weinstein, H. C., & Ostelo, R. W. (2019). Inflammatory biomarkers in patients with sciatica: a systematic review. BMC musculoskeletal disorders, 20: 1-9.
Kizilay, Z., Aktas, S., Cetin, N. K., Kilic, M. A. and Ozturk, H. (2019). Effect of Tarantula cubensis extract (Theranekron) on peripheral nerve healing in an experimental sciatic nerve injury model in rats. Turk Neurosurg, 29(5): 743-749.‏
Ma, L., Mu, Y., Zhang, Z. and Sun, Q. (2018). Eugenol promotes functional recovery and alleviates inflammation, oxidative stress, and neural apoptosis in a rat model of spinal cord injury. Restorative Neurology and Neuroscience, 36(5): 659-668.‏
Magalhães, C. B., Casquilho, N. V., Machado, M. N., Riva, D. R., Travassos, L.H., Leal-Cardoso, J.H., Fortunato, R.S., Faffe, D.S., Zin, W. A. (2019). The anti-inflammatory and anti-oxidative actions of eugenol improve lipopolysaccharide-induced lung injury. Respiratory Physiology & Neurobiology, 259:30-36.
Mishra, P. and Stringer, M. D. (2010). Sciatic nerve injury from intramuscular injection: a persistent and global problem. International journal of clinical practice, 64(11): 1573-1579.
Nelson, B. C., Johnson, M. E., Walker, M. L., Riley, K. R. and Sims, C. M. (2016). Antioxidant cerium oxide nanoparticles in biology and medicine. Antioxidants, 5(2): 15.
Oró, D., Yudina, T., Fernández-Varo, G., Casals, E., Reichenbach, V., Casals, G., Presa, B.G., Sandalinas, S., Carvajal, S., Puntes, V.,  Jiménez, W. (2016). Cerium oxide nanoparticles reduce steatosis, portal hypertension and display anti-inflammatory properties in rats with liver fibrosis. Journal of hepatology, 64(3): 691-698.
Ostelo, R. W. (2020). Physiotherapy management of sciatica. Journal of physiotherapy, 66(2): 83-88.
Park, E. J., Cho, W. S., Jeong, J., Yi, J. H., Choi, K., Kim, Y. and Park, K. (2010). Induction of inflammatory responses in mice treated with cerium oxide nanoparticles by intratracheal instillation. Journal of Health Science, 56(4): 387-396.‏
Pinto, R. Z., Maher, C. G., Ferreira, M. L., Ferreira, P. H., Hancock, M., Oliveira, V. C. and Koes, B. (2012). Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis. Bmj, 344.
Poutoglidou, F., Piagkou, M., Totlis, T., Tzika, M. and Natsis, K. (2020). Sciatic nerve variants and the piriformis muscle: a systematic review and meta-analysis. Cureus, 12(11).
Soluki, M., Mahmoudi, F., Abdolmaleki, A., Asadi, A. and Sabahi Namini, A. (2020). Cerium oxide nanoparticles as a new neuroprotective agent to promote functional recovery in a rat model of sciatic nerve crush injury. British Journal of Neurosurgery, 1-6.
Taleuzzaman, M., Jain, P., Verma, R., Iqbal, Z. and Mirza, M. (2021). Eugenol as a potential drug candidate: A review. Current Topics in Medicinal Chemistry, 21(20): 1804-1815.
Valat, J. P., Genevay, S., Marty, M., Rozenberg, S. and Koes, B. (2010). Sciatica. Best practice & research Clinical rheumatology, 24(2): 241-252.
Van Tulder, M., Peul, W. and Koes, B. (2010). Sciatica: what the rheumatologist needs to know. Nature reviews Rheumatology, 6(3): 139-145.