Keywords
active proteolytic enzymes
Cocarnit
NGF
VEGF
bFGF
Abstract
Ulcers and slow wound healing are common in diabetic polyneuropathy (DP), as well as shooting or burning pain, sensitivity to touch or lack of sensitivity, low oxygenation of nerve tissue, conductivity disorders and various vascular disorders. The mechanisms of DP development are complex and have not been completely studied. To take into account the role of B group vitamins, we investigated histological structure of nerve tissue, the level of different growth factors and the qualitative composition of active proteolytic enzymes in rats with DP and after the use of the metabolic drug Cocarnit for 9 days. This drug composition include nicotinamide, cocarboxylase, cyanocobalamin, adenosine triphosphate disodium trihydrate. We used an histological study of sciatic nerve; enzyme-linked immunosorbent assay and enzyme electrophoresis methods. In rats with DP, fragmentation of nerve tissue and their necrosis was established. Moreover, degraded forms of plasmin that has a fully functional serine proteinase domain are evident, and, therefore, it exhibits proteolytic properties. DP led to a decrease of neuron growth factor (NGF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). After treatment, the histological structure of nerve tissue was significantly improved, and the expression of growth factors NGF and bFGF was increased. Our study demonstrated that administration of Corcarnit brought about the complete restoration of the activation potential of plasmin and the almost disappearance of all degraded forms which were evident in the group with DP.References
1. Diabetes mellitus. WHO; 2010.
2. Amin N, Doupis J. Diabetic foot disease: From the evaluation of the «foot at risk» to the novel diabetic ulcer treatment modalities. World J Diabetes. 2016;7(7):153-64.
3. Volmer-Thole M, Lobmann R. Neuropathy and diabetic foot syndrome. Int J Mol Sci. 2016;17(6):E917.
4. Tatianenko LV, Bogdanov GN, Varfolomeev VN, Kotelnikova RA, Shaposhnikova GI, Smirnov LD. Structural-functional changes in biomembranes during complications of diabetes mellitus and their pharmacological correction. Vopr Med Khim. 2017;44(6):551-8.
5. Zochodne DW. Diabetes mellitus and the peripheral nervous system: Manifestations and mechanisms. Muscle Nerve. 2007;6(2):144-66.
6. Jack M, Wright DE. The role of advanced glycation endproducts and glyoxalase I in diabetic peripheral sensory neuropathy. Transl Res. 2012;159(5):355-65.
7. Grindel A, Guggenberger B, Eichberger L, Pöppelmeyer C, Gschaider M, Tosevska A, et al. Oxidative stress, DNA Damage and DNA repair in female patients with diabetes mellitus type 2. PLoS One. 2016;11(9):1-17.
8. Russell JW, Golovoy D, Vincent AM, Mahendru P, Olzmann JA, Mentzer A. High glucose-induced oxidative stress and mitochondrial dysfunction in neurons. FASEB J. 2002;16:1738-48.
9. Mehra A, Ali C, Parcq J, Vivien D, Docagne F. The plasminogen activation system in neuroinflammation. BBA - Molecular Basis of Disease. 2016;1862(3):395-402.
10. Aisina RB, Mukhametova LI. Structure and function of plasminogen/plasmin system. Russ J Bioorg Chem. 2014;40:590-605.
11. Singleton JR, Smith AG, Russell JW, Feldman EL. Microvascular complications of impaired glucose tolerance. Diabetes. 2003;52(12):2867-73.
12. Taiana MM, Lombardi R, Porretta-Serapiglia C, Ciusani E, Oggioni N, Sassone J, et al. Neutralization of Sschwann cell-secreted VEGF is protective to in vitro and in vivo experimental diabetic neuropathy. Zhou R, editor. PLoS One. 2014;9(9):e108403.
13. Brewster WJ, Fernyhough P, Diemel LT, Mohiuddin L, Tomlinson DR. Diabetic neuropathy, nerve growth factor and other neurotrophic factors. Trends Neurosci. 1994;17(8):321-5.
14. Apfel SC, Schwartz S, Adornato BT, Freeman R, Biton V, Rendell M, et al. Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy: A randomized controlled trial. rhNGF Clinical Investigator Group. JAMA. 2000;284(17):2215-21.
15. Chen S-Q, Cai Q, Shen Y-Y, Cai X-Y, Lei H-Y. Combined use of NGF/BDNF/bFGF promotes proliferation and differentiation of neural stem cells in vitro. Int J Dev Neurosci. 2014;38:74-8.
16. Abe K, Saito H. Effects of basic fibroblast growth factor on central nervous system functions. Pharmacol Res. 2001:43(4):307-12.
17. Katsuki H, Itsukaichi Y, Matsuki N. Distinct signaling pathways involved in multiple effects of basic fibroblast growth factor on cultured rat hippocampal neurons. Brain Res. 2000;885(2):240-50.
18. Grothe C, Nikkhah G. The role of basic fibroblast growth factor in peripheral nerve regeneration. Anat Embryol (Berl). 2001;204(3):171-7.
19. Fujimoto E, Mizoguchi A, Hanada K, Yajima M, Ide C. Basic fibroblast growth factor promotes extension of regenerating axons of peripheral nerve. In vivo experiments using a Schwann cell basal lamina tube model. J Neurocytol. 1997;26(8):511-28.
20. Li X, Zhang J, Zhao W, Yang H, Yang H, Ma J, Qi Y, et al. Effect of Tongxinluo on nerve regeneration in mice with diabetic peripheral neuropathy. Cell Mol Biol (Noisy-le-grand). 2015;61(5):103-7.
21. Li R, Ma J, Wu Y, Nangle M, Zou S, Li Y, et al. Dual delivery of NGF and bFGF coacervater ameliorates diabetic peripheral neuropathy via inhibiting schwann cells apoptosis. Int J Biol Sci. 2017:13(5):640-51.
22. Javed S, Petropoulos IN, Alam U, Malik RA. Treatment of painful diabetic neuropathy. Ther Adv Chronic Dis. 2015;6(1):15-28.
23. Schreiber AK. Diabetic neuropathic pain: Physiopathology and treatment. World J Diabetes. 2015;6(3):432.
24. Elgayar SA, Eltony SA, Sayed AA, Abbas AY. Protective effect of vitamin B complex in diabetic peripheral neuropathy.Histopathological study. Eur J Anat. 2017;21(3):173-87.
25. Kirichek LT. Pharmacology of vitamins. Int Med J. 2001;7(4):97-104.
26. Ang CD, Alviar MJ, Dans AL, Bautista-Velez GG, Villaruz-Sulit MV, Tan JJ, at al. Vitamin B for treating peripheral neuropathy. Cochrane Database Syst. Rev. 2008;16(3):CD004573.
27. Zhang YF, Ning G. Mecobalamin. Expert Opin Investig Drugs. 2008;17(6):953-64.
28. Roy RP, Ghosh K, Ghosh M, Acharyya A, Bhattacharya A, Pal M, Chakraborty S, Sengupta N. Study of Vitamin B12 deficiency and peripheral neuropathy in metformin-treated early Type 2 diabetes mellitus. Indian J Endocrinol Metab. 2016;20(5):631-7.
29. Head KA. Peripheral neuropathy: pathogenic mechanisms and alternative therapies. Altern Med Rev. 2006;11:294-329.
30. Andrès E, Loukili NH, Noel E. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171:251-9.
31. Liu KW, Dai LK, Jean W. Metformin-related vitamin B12 deficiency. Age Ageing. 2006;35:200-1.
32. Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B(12) deficiency in patients receiving metformin. Arch Intern Med. 2006;166:1975-9.
33. Okada K, Tanaka H, Temporin K, Okamoto M, Kuroda Y, Moritomo H, et al. Methylcobalamin increases Erk1/2 and Akt activities through the methylation cycle and promotes nerve regeneration in a rat sciatic nerve injury model. Exp Neurol. 2010;222:191-203.
34. Sun Y, Lai MS, Lu CJ. Effectiveness of vitamin B12 on diabetic neuropathy: systematic review of clinical controlled trials. Acta Neurol Taiwan. 2005;14:48-54.
35. Jayabalan B, Low LL. Vitamin B supplementation for diabetic peripheral neuropathy. Singapore Med J. 2016;57(2): 5-9.
36. Nozdrenko D, Beregovyi S, Nikitina N, Stepanova L, Beregova T, Ostapchenko L. The influence of complex drug cocarnit on the nerve conduction velocity in nerve tibialis of rats with diabetic polyneuropathy. Biomed Res. 2018;29(19):3629-34.
37. Kotov SV, Isakova EV, Leidvoll VY, Belova YuA, Volchenkova TV, Borodin AV, et al. The efficacy of cocarnit in diabetic neuropathy. Zh Nevrol Psikhiatr Im S.S. Korsakova. 2018;118(1):37-42.
38. Smelt HJM, Pouwels S, Said M, Smulders JF. Neuropathy by folic acid supplementation in a patient with anaemia and an untreated cobalamin deficiency: a case report. Clin Obes. 2018;8(4):300-4.
39. Gibson GE, Park LC, Sheu KF, Blass JP, Calingasan NY. The alpha-ketoglutarate dehydrogenase complex in neurodegeneration. Neurochem Int. 2000;36(2):97-112.
40. Hoffer A. Use of nicotinic acid and/or nicotinamide in high doses to treat schizophrenia. Can J Psychiatr Nurs. 1966;7(8):5-6.
41. Belov VG, Parfenov IA, Zaplutanov VA. Features of psychopharmacotherapeutic correction of alcohol dependence in the elderly. Adv Gerontol. 2013;26(4):702-6.
42. King AJ. The use of animal models in diabetes research. Br J Pharmacol. 2012;166(3):877-94.
43. Sarkisova DS, Perova YuL. Microscopic technique: Management. Moscow: Medicine. 1996;544.
44. Crowther JR. The ELISA guidebook. Methods Mol Biol. 2000;149: 1-413.
45. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.
46. Heussen C. Dowdle E. Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Anal Biochem. 1980;102:196-202.
47. Ostapchenko L, Savchuk O, Burlova-Vasilieva N. Enzyme electrophoresis m ethod in analysis of active components of haemostasis system. Adv Biosci Biotechnol. 2011; 2(1):20-6.
48. Harlow E. Lane D. Antibodies. Cold Spring Harbor Laboratory. New York; 1998: 726.
49. Protein Electrophoresis Technical manual. Amersham Biosciences Inc.; 1999.
50. Rebrova OYu. Statistical analysis of medical data. Application of application package STATISTICA. Moscow: Media Sph; 2002:312.
51. Yang X-W, Liu F-Q, Guo J-J, Yao W-J, Li Q-Q, Liu T-H, et al. Antioxidation and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy. BMC Complement Altern Med. 2015;15(1):66.
52. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813-20.
53. Yakobchuk SO, Ihefody AG, Kolotylo OB. Questions of the pathogenesis of diabetic neuropathy. Bukovinsky Medical Bulletin. 2012;16(63):142-5.
54. Barlow GH, Summaria L, Robbins KC. Molecular weight studies on human plasminogen and plasmin at the microgram level. J Biol Chem. 1969;244(5):1138-41.
55. Graiani G, Emanueli C, Desortes E, Linthout SV, Pinna A, Figueroa CD, et al. Nerve growth factor promotes reparative angiogenesis and inhibits endothelial apoptosis in cutaneous wounds of Type 1 diabetic mice. Diabetologia. 2004;47(6):1047-54.
56. Nozdrenko D, Berehovyi S, Nikitina N, Stepanova L,Beregova T, Ostapchenko L. The influence of complex drug cocarnit on the nerve conduction velocity in nerve tibialis of rats with diabetic polyneuropathy Biomed Res. 2018;29(19):3629-34.
57. Beregova TV, Nozdrenko DM, Beregovyi SM, Nikitina NS, Falalyeyeva TM, Ostapchenkо LI. Dynamic properties of skeletal muscle contraction in rats with diabetes. UK: St George`s Healthcare NHS Trust. 2018;7:119-39.
58. Malik RA. Pathology of human diabetic neuropathy. Clinical Neurology. 2004;249-59.
59. Yagihashi S. Pathology and pathogenetic mechanisms of diabetic neuropathy: correlation with clinical signs and symptoms. Diabetes Res Clin Pract. 2007;77(1): 184-89.
60. Pittenger G, Vinik A, Pittenger GL. Nerve growth factor and diabetic neuropathy. Exp Diab Res. 2003;4:71-85.
61. Takagi H, King GL, Ferrara N, Aiello LP. Hypoxia regulates vascular endothelial growth factor receptor KDR/Flk gene expression through adenosine A2 receptors in retinal capillary endothelial cells. Invest Ophthalmol Vis Sci. 1996;37(7):1311-21.
62. Lindberger M, Schröder HD, Schultzberg M, Kristensson K, Persson A, Ostman J, et al. Nerve fibre studies in skin biopsies in peripheral neuropathies. I. Immunohistochemical analysis of neuropeptides in diabetes mellitus. J Neurol Sci. 1989;93(2-3):289-96.
63. Apfel SC, Arezzo JC, Brownlee M, Federoff H, Kessler JA. Nerve growth factor administration protects against experimental diabetic sensory neuropathy. Brain Res. 1994;634(1):7-12.
64. Hulse RP, Beazley-Long N, Ved N, Bestall SM, Riaz H, Singhal P, et al. Vascular endothelial growth factor-A 165 b prevents diabetic neuropathic pain and sensory neuronal degeneration. Clin Sci. 2015;129(8):741-56.
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