NEUROREGENERATIVE EFFECTS OF D-Î±-TOCOPHEROL ON THE CRUSHED SCIATIC NERVE OF DIABETIC RATS
Objective: This present study is designed to explore the neuroregenerative effects of d-Î±-tocopherol on peripheral nerve in both healthy and diabetic
Methods: 24 albino rats were divided into four groups; healthy control, diabetic control, healthy treated, and diabetic treated. Diabetes was induced
by single subcutaneous injection of alloxan (100 mg/kg). Treated groups were administered d-Î±-tocopherol orally, daily (200 mg/kg) for 3 weeks.
Through a mid-thigh incision, sciatic nerve was crushed with Kocherâ€™s forceps, and skin wound was closed with absorbable suture. Sciatic functional
and static indices were used to assess the functional recovery in conjunction with histological, histomorphological, and biochemical analyses at the
end of 3 weeks.
Results: It was noticed that d-Î±-tocopherol supplementation accelerates functional recovery, enhances the antioxidant levels, and promotes the
regeneration and extracellular matrix reorganization of peripheral nerves.
Conclusion: It is concluded that the d-Î±-tocopherol appears to be an optimistic option in the management of peripheral nerve crush injury in both
healthy and diabetics.
Keywords: Antioxidant, d-Î±-tocopherol, Diabetes, Rats, Regeneration, Sciatic nerve.
1. Sireesha K, Rao SP. Oxidative stress and diabetes: And overview. Asian
J Pharm Clin Res 2015;8:15-9.
2. Bin-Jaliah I, El-Attar S, Khaleel EF, El-Sayed LA, Haidara MA.
Remedial effects of vitamin e and l-arginine on peripheral neuropathy
in streptozotocin-induced diabetic rats. Am J Pharmacol Toxicol
3. Negi G, Kumar A, Kaundal RK, Gulati A, Sharma SS. Functional
and biochemical evidence indicating beneficial effect of melatonin
and nicotinamide alone and in combination in experimental diabetic
neuropathy. Neuropharmacology 2010;58(3):585-92.
4. Merenda A, Bullock R. Clinical treatments for mitochondrial
dysfunctions after brain injury. Curr Opin Crit Care 2006;12(2):90-6.
5. LalkovicovÃ¡ M, DanielisovÃ¡ V. Neuroprotection and antioxidants.
Neural Regen Res 2016;11(6):865-74.
6. Cotter MA, Love A, Watt MJ, Cameron NE, Dines KC. Effects of
natural free radical scavengers on peripheral nerve and neurovascular
function in diabetic rats. Diabetologia 1995;38(11):1285-94.
7. Cameron NE, Cotter MA, Horrobin DH, Tritschler HJ. Effects of alphalipoic
on neurovascular function in
fatty acids. Diabetologia 1998;41(4):390-9.
8. Sen CK, Khanna S, Roy S. Tocotrienol: The natural vitamin E to defend
the nervous system? Ann N Y Acad Sci 2004;1031:127-42.
9. Khan AA, Ajmal M, Faizal MP, Elsy B, Faruqi NA. Effects of
vitamin C on regeneration of sciatic nerve crush injury\in adult rats - A
light microscopic study. J Int Acad Res Multidiscip 2015;3:68-77.
10. Khan AA, Faruqi NA, Ansari MS. Effects of hydrocortisone on the
sciatic nerve crushes injury in adult rat - A light microscopic study. Curr
11. Chalfoun CT, Wirth GA, Evans GR. Tissue engineered nerve constructs:
Where do we stand? J Cell Mol Med 2006;10(2):309-17.
12. Jiao H, Yao J, Yang Y, Chen X, Lin W, Li Y, et al. Chitosan/
polyglycolic acid nerve grafts for axon regeneration from prolonged
axotomized neurons to chronically denervated segments. Biomaterials
13. Vleggeert-Lankamp CL. The role of evaluation methods in the
assessment of peripheral nerve regeneration through synthetic
conduits: A systematic review. Laboratory investigation. J Neurosurg
14. Elsy B, Maheshwari V, Khan AA. Effects of d-Î±-tocopherol on
progression of reepithelialization, matrix remodeling and appearance
of epidermal appendages in secondary skin wounds of diabetic rats.
J Dermatol Clin Res 2016;4:1081-7.
15. Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete
sciatic, peroneal, and posterior tibial nerve lesions in the rat. Plast
Reconstr Surg 1989;83(1):129-38.
16. Bervar M. Video analysis of standing - An alternative footprint analysis
to assess functional loss following injury to the rat sciatic nerve.
J Neurosci Methods 2000;102(2):109-16.
17. Sinha AK. Colorimetric assay of catalase. Anal Biochem
18. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as
a measure of â€œantioxidant powerâ€: The FRAP assay. Anal Biochem
19. Hawkins CL, Davies MJ. Generation and propagation of radical
reactions on proteins. Biochim Biophys Acta 2001;1504(2-3):196-219.
20. Baydas G, Sonkaya E, Tuzcu M, Yasar A, Donder E. Novel role
for gabapentin in neuroprotection of central nervous system
in streptozotocine-induced diabetic rats. Acta Pharmacol Sin
21. Fan L, Yu Z, Li J, Dang X, Wang K. Schwann-like cells seeded in
acellular nerve grafts improve nerve regeneration. BMC Musculoskelet
22. Algaidi S. The effect of antioxidants on experimentally induced diabetic
peripheral neuropathy in adult male albino rats. J Am Sci 2011;7:671-7.
23. Navarro X, VivÃ³ M, Valero-CabrÃ© A. Neural plasticity after peripheral
nerve injury and regeneration. Prog Neurobiol 2007;82(4):163-201.
24. Sarikcioglu L, Demirel BM, Utuk A. Walking track analysis: An
assessment method for functional recovery after sciatic nerve injury in
the rat. Folia Morphol (Warsz) 2009;68(1):1-7.
Innovare Journal of Health Sciences, Vol 5, Issue 2, 2017, 1-6
Elsy et al.
25. de Medinaceli L, Freed WJ, Wyatt RJ. An index of the functional
condition of rat sciatic nerve based on measurements made from
walking tracks. Exp Neurol 1982;77(3):634-43.
26. Malysz T, Ilha J, Nascimento PS, De Angelis K, Schaan BD, Achaval M.
Beneficial effects of treadmill training in experimental diabetic nerve
regeneration. Clinics (Sao Paulo) 2010;65(12):1329-37.
27. Castro J, Negredo P, AvendaÃ±o C. Fiber composition of the rat
sciatic nerve and its modification during regeneration through a sieve
electrode. Brain Res 2008;1190:65-77.
28. Terada M, Yasuda H, Kikkawa R. Delayed Wallerian degeneration and
increased neurofilament phosphorylation in sciatic nerves of rats with
streptozocin-induced diabetes. J Neurol Sci 1998;155(1):23-30.
29. Terada M, Yasuda H, Kogawa S, Maeda K, Haneda M, Hidaka H, et al.
Expression and activity of cyclin-dependent kinase 5/p35 in adult rat
peripheral nervous system. J Neurochem 1998;71(6):2600-6.
30. Yasuda H, Terada M, Maeda K, Kogawa S, Sanada M, Haneda M,
et al. Diabetic neuropathy and nerve regeneration. Prog Neurobiol
31. Khan AA. Wallerian degeneration in the optic nerve of the rabbit. Cells
Tissues Organs 2004;177(2):104-9.
32. Breshah MN, Sadakah AA, Eldrieny EA, Saad KA. Functional
and histological evaluation of rat sciatic nerve anastomosis using
cyanoacrylate and fibrin glue. Tanta Dent J 2013;10:67-74.
33. Sunderland S. Nerves and Vmuz Iqtrirr. 2
ed. Edinburgh: Livingstone;
34. Tassler PL, Dellon AL, Canoun C. Identification of elastic fibres in the
peripheral nerve. J Hand Surg Br 1994;19(1):48-54.
35. Pfister BJ, Gordon T, Loverde JR, Kochar AS, Mackinnon SE,
Cullen DK. Biomedical engineering strategies for peripheral nerve
repair: Surgical applications, state of the art, and future challenges. Crit
Rev Biomed Eng 2011;39(2):81-124.
36. Grinsell D, Keating CP. Peripheral nerve reconstruction after injury:
A review of clinical and experimental therapies. BioMed Res Int
37. Sanchez EC. Hyperbaric oxygenation in peripheral nerve repair and
regeneration. Neurol Res 2007;29(2):184-98.
38. Flores AJ, Lavernia CJ, Owens PW. Anatomy and physiology of
peripheral nerve injury and repair. Am J Orthop (Belle Mead NJ)
39. Agamanolis DP. Neuropathy, An illustrated interactive course for
medical students and residents. Chapter 12, peripheral nerve pathology
40. Hobson MI. Increased vascularisation enhances axonal regeneration
within an acellular nerve conduit. Ann R Coll Surg Engl
41. Vasudevan DM, Sreekumari S. Textbook of Biochemistry (For Medical
ed. New Delhi: Jaypee Publication; 2005. p. 340-1.
42. Jeyashanthi N, Ashok V. Anti-oxidative effect of Cassia auriculata
on streptozotocin induced diabetic rats. Indian J Clin Biochem
43. Shirpoor A, Ansari MH, Salami S, Pakdel FG, Rasmi Y. Effect of
vitamin E on oxidative stress status in small intestine of diabetic rat.
World J Gastroenterol 2007;13(32):4340-4.
44. Shelat DY, Acharya SR. Neuroprotective activity of novel cur-ca-thione
and its oxidative stress study. Int J Pharm Pharm Sci 2016;8:167-73.
45. Brahm KT, Kanti BP, Abidi AB, Ibrahim RS. Markers of oxidative
stress during diabetes mellitus. J Biomark 2013;2013:3.
46. Nakhaee A, Bokaeian M, Saravani M, Farhangi A, Akbarzadeh A.
Attenuation of oxidative stress in streptozotocin-induced diabetic rats
by Eucalyptus globulus. Indian J Clin Biochem 2009;24(4):419-25.