Biological Trace Element Research

, Volume 176, Issue 2, pp 328–337 | Cite as

Selenium Ameliorate Peripheral Nerve Ischemic-Reperfusion Injury via Decreased TNF-α

  • Abolfazl Zendedel
  • Zahra Gharibi
  • Khatereh Anbari
  • Abolfazl Abbaszadeh
  • Zahra Khanipour khayat
  • Reza Mohammadrezaei Khorramabadi
  • Maryam Soleymaninejad
  • Mohammadreza Gholami


Selenium is considered as a trace element that plays antioxidant role in the body. So, the aim of this study was to evaluate the effect of selenium on ameliorating of sciatic nerve ischemia-reperfusion injury. Eighty (80) adult male Wistar rats weighing 250–300 g were used. They were divided into 10 groups (n = 8). Then, femoral vessels were obstructed by using 4/0 silk and splitknot techniques. After 3-h ischemia for all the groups, reperfusion was applied for different periods: 3, 7, 14, and 28 days. In half of each experimental group, 0.2 mg/kg selenium was injected intraperitoneally, coinciding with ischemia. After reperfusion, according to the grouping, rats were killed by using high dose of anesthetic drug and then sciatic nerve was removed and fixed. Then, tissue samples were processed and subsequently stained with hematoxylin-eosin, apoptosis, and immunohistochemistry stains. On the third day of reperfusion, the amount of TNF-α as an inflammatory marker of ischemia-reperfusion acute phase increased. On the seventh day of reperfusion, the amount of NF-кB as an apoptotic index and infiltration of mast cells increased in the tissue as a result of development of inflammation. But, on the 14th day of reperfusion, the amount of NF-кB as an apoptotic index decreased to the lowest amount. On the 28th day of reperfusion, the amount of TNF-α as an inflammatory marker decreased to its lowest level. Prescription of selenium concurrent with development of ischemia can reduce the damage caused by sciatic nerve ischemia-reperfusion.


Selenium Ischemia Sciatic nerve TNF-α 



This study was approved in the Lorestan University of Medical Sciences. Special thanks to Lorestan University of Medical Sciences for the financial support, Khorramabad, Iran. The authors thank the head and staff of Razi Herbal Drugs Research Center of Lorestan Medical University.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interests.


  1. 1.
    Abramson SB (1990) Mechanisms of action of nonsteroidal anti-inflammatory drugs and therapeutic considerations. Bull Hosp Joint Dis Orthop Inst 50(2):107–115Google Scholar
  2. 2.
    Acker CG, Flick R, Shapiro R, Scantlebury VP, Jordan ML, Vivas C, Greenberg A, Johnson JP (2002) Thyroid hormone in the treatment of post-transplant acute tubular necrosis (ATN). Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 2(1):57–61CrossRefGoogle Scholar
  3. 3.
    Acker CG, Singh AR, Flick RP, Bernardini J, Greenberg A, Johnson JP (2000) A trial of thyroxine in acute renal failure. Kidney Int 57(1):293–298. doi: 10.1046/j.1523-1755.2000.00827.x CrossRefPubMedGoogle Scholar
  4. 4.
    Alipour M, Gholami MR, Jafari Anarkooli I, Sohrabi D, Tajki J, Pourheidar M (2011) Intraperitoneal aminoguanidine improves sciatic nerve ischemia-reperfusion injury in male Sprague-dawley rats. Cell Mol Neurobiol 31(5):765–773. doi: 10.1007/s10571-011-9682-5 CrossRefPubMedGoogle Scholar
  5. 5.
    Gholami MR, Abolhassani F, Pasbakhsh P, Akbari M, Sobhani A, Eshraghian MR, Kamalian N, Amoli FA, Dehpour AR, Sohrabi D (2008) The effects of simvastatin on ischemia-reperfusion injury of sciatic nerve in adult rats. Eur J Pharmacol 590(1–3):111–114. doi: 10.1016/j.ejphar.2008.05.050 CrossRefPubMedGoogle Scholar
  6. 6.
    Gholami MR, Abolhassani F, Pasbakhsh P, Akbari M, Sobhani A, Sohrabi D, Mehrania K (2007) The effects of simvastatin on functional recovery of rat reperfused sciatic nerve. Pak J Biol Sci: PJBS 10(23):4256–4260CrossRefPubMedGoogle Scholar
  7. 7.
    Reiter RJ, Carneiro RC, Oh CS (1997) Melatonin in relation to cellular antioxidative defense mechanisms. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 29 (8):363–372. doi: 10.1055/s-2007-979057
  8. 8.
    Zollman PJ, Awad O, Schmelzer JD, Low PA (1991) Effect of ischemia and reperfusion in vivo on energy metabolism of rat sciatic-tibial and caudal nerves. Exp Neurol 114(3):315–320CrossRefPubMedGoogle Scholar
  9. 9.
    Iida H, Schmelzer JD, Schmeichel AM, Wang Y, Low PA (2003) Peripheral nerve ischemia: reperfusion injury and fiber regeneration. Exp Neurol 184(2):997–1002. doi: 10.1016/S0014-4886(03)00385-6 CrossRefPubMedGoogle Scholar
  10. 10.
    Gray C, Nukada H, Jackson DM, McMorran PD, Wu A, Ma F (2003) Neuroprotective effects of nitrone radical scavenger S-PBN on reperfusion nerve injury in rats. Brain Res 982(2):179–185CrossRefPubMedGoogle Scholar
  11. 11.
    Erbil G, Ozbal S, Sonmez U, Pekcetin C, Tugyan K, Bagriyanik A, Ozogul C (2008) Neuroprotective effects of selenium and Ginkgo biloba extract (EGb761) against ischemia and reperfusion injury in rat brain. Neurosciences 13(3):233–238PubMedGoogle Scholar
  12. 12.
    Ozbal S, Erbil G, Kocdor H, Tugyan K, Pekcetin C, Ozogul C (2008) The effects of selenium against cerebral ischemia-reperfusion injury in rats. Neurosci Lett 438(3):265–269. doi: 10.1016/j.neulet.2008.03.091 CrossRefPubMedGoogle Scholar
  13. 13.
    Gholami M, Zendedel A, Khanipour khayat Z, Ghanad K, Nazari A, Pirhadi A (2015) Selenium effect on ischemia-reperfusion injury of gastrocnemius muscle in adult rats. Biol Trace Elem Res 164(2):205–211. doi: 10.1007/s12011-014-0218-y CrossRefPubMedGoogle Scholar
  14. 14.
    AL-Rasheed NM, Attia HA, Mohamed RA, Al-Rasheed NM, Al-Amin MA (2014) Preventive effects of selenium yeast, chromium Picolinate, zinc sulfate and their combination on oxidative stress, inflammation, impaired angiogenesis and Atherogenesis in myocardial infarction in rats. Journal of Pharmacy & Pharmaceutical Sciences 16(5):848–867CrossRefGoogle Scholar
  15. 15.
    Ostadalova I, Vobecky M, Chvojkova Z, Mikova D, Hampl V, Wilhelm J, Ostadal B (2007) Selenium protects the immature rat heart against ischemia/reperfusion injury. Mol Cell Biochem 300(1–2):259–267. doi: 10.1007/s11010-006-9391-4 CrossRefPubMedGoogle Scholar
  16. 16.
    Zendedel ADS, Ahmadvand H, Ghanadi K, Gholami M (2015) Effects of selenium on antioxidant activity and recovery from sciatic nerve ischemia–reperfusion in adult rats. Zahedan. J Res Med Sci 17(12):1–6Google Scholar
  17. 17.
    Yao HD, Wu Q, Zhang ZW, Zhang JL, Li S, Huang JQ, Ren FZ, Xu SW, Wang XL, Lei XG (2013) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks. J Nutr 143(5):613–619. doi: 10.3945/jn.112.172395 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Yao HD, Wu Q, Zhang ZW, Li S, Wang XL, Lei XG, Xu SW (2013) Selenoprotein W serves as an antioxidant in chicken myoblasts. Biochim Biophys Acta 1830(4):3112–3120. doi: 10.1016/j.bbagen.2013.01.007 CrossRefPubMedGoogle Scholar
  19. 19.
    Swardfager W, Lanctot K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010) A meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry 68(10):930–941. doi: 10.1016/j.biopsych.2010.06.012 CrossRefPubMedGoogle Scholar
  20. 20.
    Gholami M, Khayat ZK, Anbari K, Obidavi Z, Varzi A, Boroujeni MB, Alipour M, Niapoor A, Gharravi AM (2016) Quercetin ameliorates peripheral nerve ischemia-reperfusion injury through the NF-kappa B pathway. Anat Sci Int. doi: 10.1007/s12565-016-0336-z PubMedGoogle Scholar
  21. 21.
    Saray A, Apan A, Kisa U (2003) Free radical-induced damage in experimental peripheral nerve injection injury. J Reconstr Microsurg 19(6):401–406. doi: 10.1055/s-2003-42637 CrossRefPubMedGoogle Scholar
  22. 22.
    Mitsui Y, Schmelzer JD, Zollman PJ, Mitsui M, Kihara M, Low PA (1999) Hypothermic neuroprotection of peripheral nerve of rats from ischemia-reperfusion injury: intraischemic vs. reperfusion hypothermia. Brain Res 827(1–2):63–69CrossRefPubMedGoogle Scholar
  23. 23.
    Wang Y, Kawamura N, Schmelzer JD, Schmeichel AM, Low PA (2008) Decreased peripheral nerve damage after ischemia-reperfusion injury in mice lacking TNF-alpha. J Neurol Sci 267(1–2):107–111. doi: 10.1016/j.jns.2007.10.004 CrossRefPubMedGoogle Scholar
  24. 24.
    Turan B, Saini HK, Zhang M, Prajapati D, Elimban V, Dhalla NS (2005) Selenium improves cardiac function by attenuating the activation of NF-κB due to ischemia-reperfusion injury. Antioxid Redox Signal 7(9–10):1388–1397CrossRefPubMedGoogle Scholar
  25. 25.
    Joseph J, Loscalzo J (2013) Selenistasis: epistatic effects of selenium on cardiovascular phenotype. Nutrients 5(2):340–358. doi: 10.3390/nu5020340 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Lee YJ, Kim JE, Kwak MH, Go J, Yang SY, Kwon HS, Kim BC, Kim JM, Hwang DY (2014) Selenium treatment significantly inhibits tumor necrosis factor-alpha-induced cell death and tau hyperphosphorylation in neuroblastoma cells. Mol Med Rep 10(4):1869–1874. doi: 10.3892/mmr.2014.2442 PubMedGoogle Scholar
  27. 27.
    Turan B (2010) Role of antioxidants in redox regulation of diabetic cardiovascular complications. Curr Pharm Biotechnol 11(8):819–836CrossRefPubMedGoogle Scholar
  28. 28.
    Bozkurt S, Arikan DC, Kurutas EB, Sayar H, Okumus M, Coskun A, Bakan V (2012) Selenium has a protective effect on ischemia/reperfusion injury in a rat ovary model: biochemical and histopathologic evaluation. J Pediatr Surg 47(9):1735–1741. doi: 10.1016/j.jpedsurg.2012.03.053 CrossRefPubMedGoogle Scholar
  29. 29.
    Heyland DK (2007) Selenium supplementation in critically ill patients: can too much of a good thing be a bad thing? Crit Care 11(4):153. doi: 10.1186/cc5975 CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Turker Y, Naziroglu M, Gumral N, Celik O, Saygin M, Comlekci S, Flores-Arce M (2011) Selenium and L-carnitine reduce oxidative stress in the heart of rat induced by 2.45-GHz radiation from wireless devices. Biol Trace Elem Res 143(3):1640–1650. doi: 10.1007/s12011-011-8994-0 CrossRefPubMedGoogle Scholar
  31. 31.
    Turker O, Karapolat I (2008) There is immunological benefit of selenium treatment in autoimmune thyroiditis. Thyroid: Off J Am Thyroid Assoc 18(6):671–672 . doi: 10.1089/thy.2007.0391author reply 673-674CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Abolfazl Zendedel
    • 1
    • 2
  • Zahra Gharibi
    • 3
  • Khatereh Anbari
    • 4
  • Abolfazl Abbaszadeh
    • 5
  • Zahra Khanipour khayat
    • 5
  • Reza Mohammadrezaei Khorramabadi
    • 6
  • Maryam Soleymaninejad
    • 7
  • Mohammadreza Gholami
    • 1
    • 3
  1. 1.Razi Herbal Medicines Research CenterLorestan University of Medical SciencesKhorramabadIran
  2. 2.Department of Internal MedicineLorestan University of Medical SciencesKhorramabadIran
  3. 3.Department of Anatomical SciencesLorestan University of Medical SciencesKhorramabadIran
  4. 4.Department of Social MedicineLorestan University of Medical SciencesKhorramabadIran
  5. 5.Department of SurgeryLorestan University of Medical SciencesKhorramabadIran
  6. 6.Student Research CommitteeLorestan University of Medical SciencesKhorramabadIran
  7. 7.Faculty of MedicineBabol University of Medical SciencesBabolIran

Personalised recommendations