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Coenzyme Q10 Influences on the Levels of TNF-α and IL-10 and the Ratio of Bax/Bcl2 in a Menopausal Rat Model Following Lumbar Spinal Cord Injury

  • Sajad Hassanzadeh
  • Seyed Behnamedin Jameie
  • Maryam Soleimani
  • Mona Farhadi
  • Mahdieh Kerdari
  • Navid Danaei
Article
  • 1 Downloads

Abstract

The roles of the immune response and apoptosis as potential mediators of secondary damage in spinal cord injury (SCI) are being investigated. Research is also being done to determine the effects of female gonadal steroids, which decrease during menopause, and antioxidants, such as coenzyme Q10 (CoQ10) on SCI. We hypothesized that in the absence of female gonadal steroids, which provide protection following an SCI, CoQ10 could modulate the expression of cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-10, besides aquaporin-4 (AQP4) water channels in the CNS, which participate in neuroinflammation, as well as the Bax and Bcl2 proteins that are involved in apoptosis at the site of injury. The spinal cord was compressed at the level of the T10 vertebrae and rats were treated by 10 mg/kg/day CoQ10 for 3 weeks after surgery. The TNF-α and IL-10 expressions were studied using an ELISA. Western blot was used to investigate the Bax/Bcl-2 ratio, AQP4. The level of TNF-α significantly decreased following the administration of CoQ10 compared with the level of IL-10. When the treatment group was compared with the OVX-SCI group, the ratio of Bax/Bcl2 significantly decreased in the groups (P < 0.01). Based on our findings, CoQ10 could be used to compensate for the absence of the neuroprotection effects provided by female gonadal steroids via reducing the inappropriate effects of the two main pathways of secondary damage in SCI apoptosis.

Keywords

Coenzyme Q10 TNF-α IL-10 Ovariectomy Spinal cord injury 

Notes

Acknowledgments

The authors acknowledge the technical assistance of the staff of the NRC of IUMS and the Research Laboratory of the Medical Basic Sciences Department, Faculty of Allied Medicine, and IUMS.

Funding information

This study received financial support from the Vice Chancellor of Research of University of Social Welfare and Rehabilitation Sciences. Research project contract number (801/94/T/14123).

References

  1. Basso DM, Beattie MS, Bresnahan JC (1995) A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12:1–21CrossRefPubMedGoogle Scholar
  2. Bethea JR et al (1999) Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma 16:851–863CrossRefPubMedGoogle Scholar
  3. Cao Y, Wu T, Li D, Ni S, Hu J, Lu H (2015) Three-dimensional imaging of microvasculature in the rat spinal cord following injury. Sci Rep 5:12643CrossRefPubMedPubMedCentralGoogle Scholar
  4. Chaovipoch P, Jelks KAB, Gerhold LM, West EJ, Chongthammakun S, Floyd CL (2006) 17 β-estradiol is protective in spinal cord injury in post-and pre-menopausal rats. J Neurotrauma 23:830–852CrossRefPubMedGoogle Scholar
  5. Charriaut-Marlangue C (2004) Apoptosis: a target for neuroprotection. Therapie 59:185–190CrossRefPubMedGoogle Scholar
  6. Coyle DE, Sehlhorst CS, Behbehani MM (1996) Intact female rats are more susceptible to the development of tactile allodynia than ovariectomized female rats following partial sciatic nerve ligation (PSNL). Neurosci Lett 203:37–40CrossRefPubMedGoogle Scholar
  7. Ekshyyan O, Aw TY (2004a) Apoptosis in acute and chronic neurological disorders. Front Biosci 9:1567–1576CrossRefPubMedGoogle Scholar
  8. Ekshyyan O, Aw TY (2004b) Apoptosis: a key in neurodegenerative disorders. Curr Neurovasc Res 1:355–371CrossRefPubMedGoogle Scholar
  9. Esposito E, Cuzzocrea S (2011) Anti-TNF therapy in the injured spinal cord. Trends Pharmacol Sci 32:107–115CrossRefPubMedGoogle Scholar
  10. Fu ES, Saporta S (2005) Methylprednisolone inhibits production of interleukin-1β and interleukin-6 in the spinal cord following compression injury in rats. J Neurosurg Anesthesiol 17:82–85CrossRefPubMedGoogle Scholar
  11. Genovese T, Mazzon E, Crisafulli C, Di Paola R, Muià C, Bramanti P, Cuzzocrea S (2006) Immunomodulatory effects of etanercept in an experimental model of spinal cord injury. J Pharmacol Exp Ther 316:1006–1016CrossRefPubMedGoogle Scholar
  12. Groves N (2011) CoQ10 may target early apoptosisGoogle Scholar
  13. Habgood M et al (2007) Changes in blood–brain barrier permeability to large and small molecules following traumatic brain injury in mice. Eur J Neurosci 25:231–238CrossRefPubMedGoogle Scholar
  14. Haggerty AE, Maldonado-Lasuncion I, Oudega M (2018) Biomaterials for revascularization and immunomodulation after spinal cord injury Biomedical MaterialsGoogle Scholar
  15. Hajimashhadi Z, Aboutaleb N, Nasirinezhad F (2017) Chronic administration of [Pyr 1] apelin-13 attenuates neuropathic pain after compression spinal cord injury in rats. Neuropeptides 61:15–22CrossRefPubMedGoogle Scholar
  16. Hou T-t, Yang X-y, Xia P, Pan S, Liu J, Qi Z-p (2015) Exercise promotes motor functional recovery in rats with corticospinal tract injury: anti-apoptosis mechanism. Neural Regen Res 10:644CrossRefPubMedPubMedCentralGoogle Scholar
  17. Hwang J-Y, Min S-W, Jeon Y-T, Hwang J-W, Park S-H, Kim J-H, Han S-H (2015) Effect of coenzyme Q10 on spinal cord ischemia-reperfusion injury. J Neurosurg Spine 22:432–438CrossRefPubMedGoogle Scholar
  18. Kerimoğlu A, Paşaoğlu O, Kanbak G, Hanci V, Ozdemir F, Atasoy MA (2007) Efficiency of coenzyme Q (10) at experimental spinal cord injury Ulusal travma ve acil cerrahi dergisi=. Turkish J Trauma Emerg Surg: TJTES 13:85–93Google Scholar
  19. Kimura A, Hsu M, Seldin M, Verkman AS, Scharfman HE, Binder DK (2010) Protective role of aquaporin-4 water channels after contusion spinal cord injury. Ann Neurol 67:794–801PubMedGoogle Scholar
  20. Lacroix S, Chang L, Rose-John S, Tuszynski MH (2002) Delivery of hyper-interleukin-6 to the injured spinal cord increases neutrophil and macrophage infiltration and inhibits axonal growth. J Comp Neurol 454:213–228CrossRefPubMedGoogle Scholar
  21. Lammertse DP (2004) Update on pharmaceutical trials in acute spinal cord injury. Taylor & Francis, 27, 319, 325,Google Scholar
  22. Lim PA, Tow AM (2007) Recovery and regeneration after spinal cord injury: a review and summary of recent literature. Ann Acad Med Singap 36:49PubMedGoogle Scholar
  23. Liu D et al. (2018) Biodegradable spheres protect traumatically injured spinal cord by alleviating the glutamate-induced excitotoxicity Advanced MaterialsGoogle Scholar
  24. Massetti J, Stein DM (2018) Spinal cord injury. In: Neurocritical care for the advanced practice clinician. Springer, pp 269–288Google Scholar
  25. Okada S, Nakamura M, Mikami Y, Shimazaki T, Mihara M, Ohsugi Y, Iwamoto Y, Yoshizaki K, Kishimoto T, Toyama Y, Okano H (2004) Blockade of interleukin-6 receptor suppresses reactive astrogliosis and ameliorates functional recovery in experimental spinal cord injury. J Neurosci Res 76:265–276CrossRefPubMedGoogle Scholar
  26. Oyinbo CA (2011) Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars) 71:281–299Google Scholar
  27. Ozturk AM, Sozbilen MC, Sevgili E, Dagci T, Özyalcin H, Armagan G (2018) Epidermal growth factor regulates apoptosis and oxidative stress in a rat model of spinal cord injury InjuryGoogle Scholar
  28. Palan PR, Connell K, Ramirez E, Inegbenijie C, Gavara RY, Ouseph JA, Mikhail MS (2005) Effects of menopause and hormone replacement therapy on serum levels of coenzyme Q_ {10} and other lipid-soluble antioxidants. Biofactors 25:61–66CrossRefPubMedGoogle Scholar
  29. Pan JZ, Ni L, Sodhi A, Aguanno A, Young W, Hart RP (2002) Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion. J Neurosci Res 68:315–322CrossRefPubMedGoogle Scholar
  30. Parihar M, Hemnani T (2004) Alzheimer’s disease pathogenesis and therapeutic interventions. J Clin Neurosci 11:456–467CrossRefPubMedGoogle Scholar
  31. Paxinos G (2007) Atlas of the developing mouse brain: At e17. 5, po, and. Academic Press,Google Scholar
  32. Pineau I, Lacroix S (2007) Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the cell types involved. J Comp Neurol 500:267–285CrossRefPubMedGoogle Scholar
  33. Plunkett JA, Yu C-G, Easton JM, Bethea JR, Yezierski RP (2001) Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat. Exp Neurol 168:144–154CrossRefPubMedGoogle Scholar
  34. Poon PC, Gupta D, Shoichet MS, Tator CH (2007) Clip compression model is useful for thoracic spinal cord injuries: histologic and functional correlates. Spine 32:2853–2859CrossRefPubMedGoogle Scholar
  35. Prokai-Tatrai K, Prokai L (2009) Prodrugs of thyrotropin-releasing hormone and related peptides as central nervous system agents. Molecules 14:633–654CrossRefPubMedGoogle Scholar
  36. Saadoun S, Bell BA, Verkman A, Papadopoulos MC (2008) Greatly improved neurological outcome after spinal cord compression injury in AQP4-deficient mice. Brain 131:1087–1098CrossRefPubMedGoogle Scholar
  37. Sandhir R, Sethi N, Aggarwal A, Khera A (2014) Coenzyme Q10 treatment ameliorates cognitive deficits by modulating mitochondrial functions in surgically induced menopause. Neurochem Int 74:16–23CrossRefPubMedGoogle Scholar
  38. Sarkaki AR, Khaksari Haddad M, Soltani Z, Shahrokhi N, Mahmoodi M (2013) Time-and dose-dependent neuroprotective effects of sex steroid hormones on inflammatory cytokines after a traumatic brain injury. J Neurotrauma 30:47–54CrossRefPubMedGoogle Scholar
  39. Shahrokhi N, Haddad MK, Joukar S, Shabani M, Keshavarzi Z, Shahozehi B (2012) Neuroprotective antioxidant effect of sex steroid hormones in traumatic brain injury. Pak J Pharm Sci 25:219–225PubMedGoogle Scholar
  40. Soleimani M, Jameie SB, Barati M, Mehdizadeh M, Kerdari M (2014a) Effects of coenzyme Q10 on the ratio of TH1/TH2 in experimental autoimmune encephalomyelitis model of multiple sclerosis in C57BL/6. Iran Biomed J 18:203PubMedPubMedCentralGoogle Scholar
  41. Soleimani M, Jameie SB, Mehdizadeh M, Keradi M, Masoumipoor M, Mehrabi S (2014b) Vitamin D3 influence the Th1/Th2 ratio in C57BL/6 induced model of experimental autoimmune encephalomyelitis. Iranian J Basic Med Sci 17:785Google Scholar
  42. Spindler M, Beal MF, Henchcliffe C (2009) Coenzyme Q10 effects in neurodegenerative disease. Neuropsychiatr Dis Treat 5:597PubMedPubMedCentralGoogle Scholar
  43. Taoka Y, Okajima K, Uchiba M, Johno M (2001) Methylprednisolone reduces spinal cord injury in rats without affecting tumor necrosis factor-α production. J Neurotrauma 18:533–543CrossRefPubMedGoogle Scholar
  44. Wingrave JM, Schaecher KE, Sribnick EA, Wilford GG, Ray SK, Hazen-Martin DJ, Hogan EL, Banik NL (2003) Early induction of secondary injury factors causing activation of calpain and mitochondria-mediated neuronal apoptosis following spinal cord injury in rats. J Neurosci Res 73:95–104CrossRefPubMedGoogle Scholar
  45. Wise PM (2002) Estrogens and neuroprotection. Trends in Endocrinol Metab 13:229–230CrossRefGoogle Scholar
  46. Wise PM, Dubal DB, Wilson ME, Rau SW, Böttner M (2001) Minireview: neuroprotective effects of estrogen—new insights into mechanisms of action. Endocrinology 142:969–973CrossRefPubMedGoogle Scholar
  47. Xu J, Fan G, Chen S, Wu Y, Xu XM, Hsu CY (1998) Methylprednisolone inhibition of TNF-α expression and NF-kB activation after spinal cord injury in rats. Mol Brain Res 59:135–142CrossRefPubMedGoogle Scholar
  48. Zamani M, Katebi M, Mehdizadeh M, Mohamadzadeh F, Soleimani M (2012) Coenzyme Q10 protects hippocampal neurons against ischemia/reperfusion injury via modulation of BAX/Bcl-2 expression. Basic and. Clin Neurosci 3:5–10Google Scholar
  49. Zhang N, Yin Y, Xu S-J, Wu Y-P, Chen W-S (2012) Inflammation & apoptosis in spinal cord injury. Indian J Med Res 135:287PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Neuroscience Research Center (NRC)Iran University of Medical SciencesTehranIran
  2. 2.Department of Anatomy, Faculty of MedicineIran University of Medical SciencesTehranIran
  3. 3.Department of Medical Basic SciencesFaculty of Allied Medicine, Iran University of Medical SciencesTehranIran
  4. 4.Department of Medical Basic SciencesUniversity of Social Welfare and Rehabilitation SciencesTehranIran
  5. 5.Department of MicrobiologyIslamic Azad UniversityKarajIran
  6. 6.Department of PediatricSemnan University of Medical SciencesSemnanIran

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