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Abstract:   (318 Views)
Introduction: Diabetic neuropathy is a common complication of diabetes mellitus. It is associated to nerve damage due to oxidative stress and high levels of pro-inflammatory mediators. In the present study, we examined the anti-nociceptive effects of Fullerene nanoparticle, as a potent anti-oxidant, during diabetic neuropathy.
Methods: Diabetes mellitus induced through injection of stereptozotocin (STZ) (40 mg/kg). Four groups used in the study as follows: the control, control+fullerene, diabetes, and diabetes mellitus+fullerene groups. All four groups received sesame oil. Treatment rats received fullerene C60 (1mg/kg/day) for 9 weeks by intra-gastric gavage. Then, cold allodynia, histology and tumor necrosis factor-α (TNF- α) protein expression of the hippocampus measured on 9 weeks after injection of STZ.
Results: Our data revealed that STZ induces cold allodynia in both hind paw and increases the TNF- α protein expression in the hippocampus. Furthermore, STZ induces neural degeneration of hippocampus. Additionally, fullerene C60 significantly attenuated cold allodynia and TNF- α protein expression. Also, fullerene C60 have neuro-protective effects on hippocampal neurons. However, fullerene C60 did not significantly reduce serum glucose level in diabetic animals.
Conclusion: Our data suggest that fullerene C60 likely suppressed pain, and neural loss of hippocampus by inhibitory effects on TNF- α protein expression in the hippocampus during diabetes.
     

References
1. Askary-Ashtiani A, Ghanjal A, Motaqi M, Meftahi GH, Hatef B, Niknam H. The isokinetic and electromyographic assessment of knee muscles strength in the short- and long-term type 2 diabetes. Asian J Sports Med. 2016; 7: 37008. [DOI:10.5812/asjsm.37008]
2. Bahari Z, Manaheji H, Hosseinmardi N, Meftahi GH, Sadeghi M, Danialy S, et al. Induction of spinal long-term synaptic potentiation is sensitive to inhibition of neuronal NOS in L5 spinal nerve-transected rats. EXCLI J. 2014; 13: 751-60.
3. Bayatpoor ME, Mirzaee S, Karami Abd M, Mohammadi MT, Shahyad S, Bahari Z, et al. Crocin treatment decreased pancreatic atrophy, LOX-1 and RAGE mRNA expression of pancreas tissue in cholesterol-fed and streptozotocin-induced diabetic rats. J Complement Integr Med. 2019; 20190117. [DOI:10.1515/jcim-2019-0117]
4. Callaghan BC, Cheng HT, Stables CL, Smith AL, Feldman EL. Diabetic neuropathy: clinical manifestations and current treatments. Lancet Neurol. 2012; 11: 521-34. [DOI:10.1016/S1474-4422(12)70065-0]
5. Choi Y, Yoon YW, Na HS, Kim SH, Chung JM. Behavioural signs of ongoing pain, cold allodynia in a rat model of neuropathic pain. Pain. 1994; 59: 369-76. [DOI:10.1016/0304-3959(94)90023-X]
6. Covey WC, Ignatowski TA, Knight PR, Spengler RN. Brain-derived TNFα: involvement in neuroplastic changes implicated in the conscious perception of persistent pain. Brain Res. 2000; 859: 113-22. [DOI:10.1016/S0006-8993(00)01965-X]
7. del Rey A, Yau HJ, Randolf A, Centeno MV, Wildmann J, Martina M, et al. Chronic neuropathic pain-like behavior correlates with IL-1b expression and disrupts cytokine interactions in the hippocampus. Pain. 2011; 152:2827-35. [DOI:10.1016/j.pain.2011.09.013]
8. Debnath M, Agrawal S. Diabetic neuropathy: oxidative and neuroinflammation. EJPMR. 2016; 3: 237-41.
9. Duarte JMN. Metabolic alterations associated to brain dysfunction in diabetes. Aging Dis. 2015; 6: 304-21. [DOI:10.14336/ad.2014.1104]
10. Farshid AA, Tamaddonfard E. Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats. Avicenna J Phytomed. 2015; 5: 469-78.
11. Feldman EL, Nave KA, Jensen TS, Bennett DLH. New horizons in diabetic neuropathy: mechanisms, bioenergetics, and pain. Neuron. 2017; 93: 1296-1313. [DOI:10.1016/j.neuron.2017.02.005]
12. Fischer R, Maier O. Interrelation of oxidative stress and inflammation in neurodegenerative disease: role of TNF. Oxid Med Cell Longev. 2015; 2015: 610813. [DOI:10.1155/2015/610813]
13. Hadipour M, Bahari Z, Afarinesh MR, Jangravi Z, Shirvani H, Meftahi GH. Administering crocin ameliorates anxiety‐like behaviors and reduces the inflammatory response in amyloid‐beta induced neurotoxicity in rat. Clin Exp Pharmacol Physiol. 2021. [DOI:10.1111/1440-1681.13494]
14. Husseini Y, Sahraei H, Meftahi GH, Dargahian M, Mohammadi A, Hatef B, et al. Analgesic and anti-inflammatory activities of hydro-alcoholic extract of Lavandula officinalis in mice: possible involvement of the cyclooxygenase type 1 and 2 enzymes. Revista Brasileira de Farmacognosia. 2016; 26: 102-8. [DOI:10.1016/j.bjp.2015.10.003]
15. Ignatowski TA, Covey WC, Knight PR, Severin CM, Nickola TJ, Spengler RN. Brain-derived TNFα mediates neuropathic pain. Brain Res. 1999; 841: 70-7. [DOI:10.1016/S0006-8993(99)01782-5]
16. Ignatowski TA, Spengler RN. Targeting tumor necrosis factor in the brain relieves neuropathic pain. World J Anesthesiol. 2018; 7: 10-9. [DOI:10.5313/wja.v7.i2.10]
17. Ismail CAN, Abd Aziz CB, Suppian R, Long I. Imbalanced oxidative stress and pro-inflammatory markers differentiate the development of diabetic neuropathy variants in streptozotocin-induced diabetic rats. J Diabetes Metab Disord. 2018; 17: 129-36. [DOI:10.1007/s40200-018-0350-x]
18. Kuhad A, Chopra K. Tocotrienol attenuates oxidative-nitrosative stress and inflammatory cascade in experimental model of diabetic neuropathy. Neuropharmacology. 2009; 57: 456-62. [DOI:10.1016/j.neuropharm.2009.06.013]
19. Liu MG, Chen J. Roles of the hippocampal formation in pain information processing. Neurosci Bull. 2009; 25: 237-66. [DOI:10.1007/s12264-009-0905-4]
20. Liu Y, Zhou LJ, Wang X, Li D, Ren WJ, Peng J, Peng G, et al. TNF-α differentially regulates synaptic plasticity in the hippocampus and spinal cord by microglia-dependent mechanisms after peripheral nerve injury. J Neurosci. 2017; 37: 871-81. [DOI:10.1523/JNEUROSCI.2235-16.2016]
21. Ling Q, Liu M, Wu MX, Xu Y, Yang J, Huang HH, et al. Anti-allodynic and neuroprotective effects of koumine, a benth alkaloid, in a rat model of diabetic neuropathy. Biol Pharm Bull. 2014; 37: 858-64. [DOI:10.1248/bpb.b13-00843]
22. Mangaiarkkarasi A, Rameshkannan S, Meher Ali R. Effect of gabapentin and pregabalin in rat model of taxol induced neuropathic pain. JCDR. 2015; 9: 11-14. [DOI:10.7860/JCDR/2015/13373.5955]
23. Mohd Shafri MA, Mat Jais AM, Mohamed F. Cresyl violet staining to assess neuroprotective and neuroregenerative effects of haruan traditional extract against neurodegenerative damage of ketamine. Int J Pharm Pharm Sci. 2012; 4: 163-8.
24. Negi G, Kumar A, Sharma SS. Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF‐κB and Nrf2 cascades. J Pineal Res. 2011; 50: 124-31. [DOI:10.1111/j.1600-079X.2010.00821.x]
25. Oyenihi AB, Ayeleso AO, Mukwevho E, Masola B. Antioxidant strategies in the management of diabetic neuropathy. Biomed Res Int. 2015; 2015: 515042. [DOI:10.1155/2015/515042]
26. Rasouli Vani J, Mohammadi MT, Sarami Foroshani M, Jafari M. Polyhydroxylated fullerene nanoparticles attenuate brain infarction and oxidative stress in rat model of ischemic stroke. EXCLI J. 2016; 15: 378-90.
27. Romero-Grimaldi C, Berrocoso E, Alba-Delgado C, Madrigal GLM, Perez-Nievas BG, Leza JC, et al. Stress increases the negative effects of chronic pain on hippocampal neurogenesis. Anesth Analg. 2015; 121: 1078-88. [DOI:10.1213/ANE.0000000000000838]
28. Satoh J, Yagihashi S, Toyota T. The possible role of tumor necrosis factor-α in diabetic polyneuropathy. Experimental Diab Res. 2003; 4: 65-71. [DOI:10.1155/EDR.2003.65]
29. Sandireddy R, Yerra VG, Areti A, Komirishetty P, Kumar A. Neuroinflammation and oxidative stress in diabetic neuropathy: futuristic strategies based on these targets. Int J Endocrinol. 2014; 2014: 674987. [DOI:10.1155/2014/674987]
30. Sarami Foroshani M, Mohammadi MT. Functionalized fullerene materials (fullerol nanoparticles) reduce brain injuries during cerebral ischemia-reperfusion in rat. JPHS. 2016; 4: 15-21.
31. Schleicher E, Friess U. Oxidative stress, AGE, and atherosclerosis. Kidney Int. 2007; 106: 17-26. [DOI:10.1038/sj.ki.5002382]
32. Schreiber AK, Nones CFM, Reis RC, Chichorro JG, Cunha JM. Diabetic neuropathic pain: physiopathology and treatment. World J Diabetes. 2015; 6: 432-44. [DOI:10.4239/wjd.v6.i3.432]
33. Sha J, Sui B, Su X, Meng Q, Zhang C. Alteration of oxidative stress and inflammatory cytokines induces apoptosis in diabetic nephropathy. Mol Med Rep. 2017; 16: 7715-23. [DOI:10.3892/mmr.2017.7522]
34. Solleiro-Villavicencio H, Rivas-Arancibia S. Effect of chronic oxidative stress on neuroinflammatory response mediated by CD4+T cells in neurodegenerative diseases. Front Cell Neurosci. 2018; 12: 114. [DOI:10.3389/fncel.2018.00114]
35. Xu GY, Li G, Liu N, Mae Huang LY. Mechanisms underlying purinergic P2X3 receptormediated mechanical allodynia induced in diabetic rats. Mol Pain. 2011; 7: 60. [DOI:10.1186/1744-8069-7-60]
36. Yang E, Gavini K, Bhakta A, Dhanasekaran M, Khan I, Parameshwaran K. Streptozotocin induced hyperglycemia stimulates molecular signaling that promotes cell cycle reentry in mouse hippocampus. Life Sci. 2018; 205: 131-5. [DOI:10.1016/j.lfs.2018.05.019]
37. Zhu GC, Tsai KL, Chen YW, Hung CH. Neural mobilization attenuates mechanical allodynia and decreases proinflammatory cytokine concentrations in rats with painful diabetic neuropathy. Phys Ther. 2018; 98: 214-22. [DOI:10.1093/ptj/pzx124]

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