Pre- and post-traumatic boric acid therapy prevents oxidative stress-mediated neuronal apoptosis in spinal cord injury

Document Type : Original Article

Authors

1 Department of Neurosurgery, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey

2 Department of Biochemistry, Demiroglu Bilim University, Medical Faculty, Istanbul, Turkey

3 Department of Neurosurgery, Eskişehir Yunus Emre State

4 Department of Medical Biochemistry, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey

5 Department of Medical Laboratory Techniques, Eldivan Health Services Vocational School, Cankırı Karatekin University, Cankırı, Turkey

6 Department of Histology and Embryology, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, Turkey

Abstract

Objective(s): In our study, the neuroprotective efficacy of pre- and post-traumatic applications of boric acid (BA) in rats with experimentally induced spinal cord injury (SCI) was investigated.
Materials and Methods: The experimental animals were divided into four groups: control group (C), SCI group (SCI), BA-treated group before SCI (BA+SCI), and BA-treated group after SCI (SCI+BA). Forty-eight hours after SCI, biochemical levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and cytochrome c (Cytc) and caspase-3 (Casp3) expressions were measured in the spinal cord tissues and were examined histologically.
Results: After SCI, oxidative stress markers, such as MDA, TOS, and OSI, and apoptosis markers Cytc and Casp3 showed an increase in levels compared to Group C. The oxidative stress markers that increased after SCI decreased with BA+SCI application, while Cytc level, one of the apoptosis markers that increased after SCI, decreased in both groups with BA application. Cell, myelin, ependymal damage, and hemorrhage levels increased after SCI compared to Group C. These histological markers increased after SCI and decreased after BA+SCI. BA was found to reduce SCI-induced oxidative stress and oxidative stress-induced apoptosis.
Conclusion: BA administered before SCI was shown to be more effective in protecting neural damage.

Keywords

Main Subjects

References

1. Smith E, Fitzpatrick P, Murtagh J, Lyons F, Morris S, Synnott K. Epidemiology of traumatic spinal cord injury in Ireland, 2010-2015. Neuroepidemiology 2018; 51: 19-24.
2. Halvorsen A, Pettersen A, Nilsen S, Halle KK, Schaanning EE, Rekand T. Epidemiology of traumatic spinal cord injury in Norway in 2012–2016: a registry-based cross-sectional study. Spinal Cord 2019; 57: 331-338.
3. Lu Y, Shang Z, Zhang W, Pang M, Hu X, Dai Y, et al. Global incidence and characteristics of spinal cord injury since 2000–2021: a systematic review and meta-analysis. BMC Med 2024; 22:285-298.
4. Marcon RM, Barros Filho TEPd, Oliveira RP, Cristante AF, Taricco MA, Colares G, et al. Experimental study on the action of methylprednisolone on Wistar rats before spinal cord injury. Acta Ortopédica Brasileira 2010; 18: 26-30.
5. Silva NA, Sousa N, Reis RL, Salgado AJ. From basics to clinical: A comprehensive review on spinal cord injury. Prog Neurobiol 2014; 114: 25-57.
6. Fatima G, Sharma V, Das S, Mahdi A. Oxidative stress and antioxidative parameters in patients with spinal cord injury: Implications in the pathogenesis of disease. Spinal cord 2015; 53: 3-6.
7. Ma Y, Li P, Ju C, Zuo X, Li X, Ding T, et al. Photobiomodulation attenuates neurotoxic polarization of macrophages by inhibiting the notch1-HIF-1α/NF-κB signaling pathway in mice with spinal cord injury. Front Immunol 2022; 13: 816952-816968.
8. Chen M, Chen S, Lin D. Carvedilol protects bone marrow stem cells against hydrogen peroxide-induced cell death via PI3K-AKT pathway. Biomed Pharmacother 2016; 78: 257-263.
9. Dimitrijevic MR, Danner SM, Mayr W. Neurocontrol of movement in humans with spinal cord injury. Artif Organs 2015; 39: 823-833.
10. Shah AA, Gupta A. Antioxidants in health and disease with their capability to defend pathogens that attack apple species of Kashmir. Plant Antioxid Health 2020; 6: 1-26.
11. Wingrave JM, Schaecher KE, Sribnick EA, Wilford GG, Ray SK, Hazen‐Martin DJ, et al. Early induction of secondary injury factors causing activation of calpain and mitochondria‐mediated neuronal apoptosis following spinal cord injury in rats. J Neurosci Res 2003; 73:95-104.
12. D’Autréaux B, Toledano MB. ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 2007; 8: 813-824.
13. Ataizi ZS, Ozkoc M, Kanbak G, Karimkhani H, Donmez DB, Ustunisik N, et al. Evaluation of the neuroprotective role of boric acid in preventing traumatic brain injury-mediated oxidative stress. Turk Neurosurg 2021; 31: 25692-25618.25694.
14. Sogut I, Oglakci A, Kartkaya K, Ol KK, Sogut MS, Kanbak G, et al. Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome. Exp Ther Med 2015; 9: 1023-1027.
15. Huang W, King V, Curran O, Dyall S, Ward R, Lal N, et al. A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury. Brain 2007; 130: 3004-3019.
16. Yazihan N, Uzuner K, Salman B, Vural M, Koken T, Arslantas A. Erythropoietin improves oxidative stress following spinal cord trauma in rats. Injury 2008; 39: 1408-1413.
17. Emery E, Aldana P, Bunge MB, Puckett W, Srinivasan A, Keane RW, et al. Apoptosis after traumatic human spinal cord injury. J Neurosurg 1998; 89: 911-920.
18. Sogut I, Paltun SO, Tuncdemir M, Ersoz M, Hurdag C. The antioxidant and antiapoptotic effect of boric acid on hepatoxicity in chronic alcohol-fed rats. Can J Physiol Pharmacol 2018; 96: 404-411.
19. Hacioglu C, Kar F, Kacar S, Sahinturk V, Kanbak G. High concentrations of boric acid trigger concentration-dependent oxidative stress, apoptotic pathways and morphological alterations in DU-145 human prostate cancer cell line. Biol Trace Elem Res 2020; 193: 400-409.
20. Friedlander RM. Apoptosis and caspases in neurodegenerative diseases. N Engl J Med 2003; 348:1365-1375.
21. Schwarz TL. Mitochondrial trafficking in neurons. Cold Spring Harb Perspect Biol 2013; 5: a011304-011319.
22. Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury. Biochim Biophys Acta 2012; 1822: 675-684.
23. Resnick DK. Topic Foreword. Neurosurgery 2013; 72: 1.
24. Center SL. Spinal cord injury (SCI) 2016 facts and figures at a glance. J Spinal Cord Med 2016; 39:4 93-494.
25. Hacıoğlu C, Kar F, Şentürk H, Kanbak G. Effects of boric acid on electrolyte balance and lipid profile against renal ischemia reperfusion injury. Biol Divers Conserv 2018; 11: 76-81.
26. Kar F, Hacioglu C, Senturk H, Donmez DB, Kanbak G. The role of oxidative stress, renal inflammation, and apoptosis in post ischemic reperfusion injury of kidney tissue: The protective effect of dose-dependent boric acid administration. Biol Trace Elem Res 2020; 195: 150-158.
27. Ross IB, Tator CH. Spinal cord blood flow and evoked potential responses after treatment with nimodipine or methylprednisolone in spinal cord-injured rats. Neurosurgery 1993; 33: 470-477.
28. Anjum A, Yazid MDi, Fauzi Daud M, Idris J, Ng AMH, Selvi Naicker A, et al. Spinal cord injury: Pathophysiology, multimolecular interactions, and underlying recovery mechanisms. Int J Mol Sci 2020; 21:7533-7567.
29. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358.
30. Huntemer-Silveira A, Patil N, Brickner MA, Parr AM. Strategies for oligodendrocyte and myelin repair in traumatic CNS injury. Front Cell Neurosci 2021; 14: 619707-619727.
31. Smith PM, Jeffery ND. Histological and ultrastructural analysis of white matter damage after naturally‐occurring spinal cord injury. Brain Pathol 2006; 16: 99-109.
32. Yu C, Gui F, Huang Q, Luo Y, Zeng Z, Li R, et al. Protective effects of muscone on traumatic spinal cord injury in rats. Ann Transl Med 2022; 10: 685-700.
33. Yao R, Ren L, Wang S, Zhang M, Yang K. Euxanthone inhibits traumatic spinal cord injury via antioxidative stress and suppression of p38 and PI3K/Akt signaling pathway in a rat model. Transl Neurosci 2021; 12: 114-126.
34. Nielsen FH. Is Boron nutritionally relevant? Nutr Rev 2008; 66: 183-191.
35. Penland JG. The importance of boron nutrition for brain and psychological function. Biol Trace Elem Res 1998; 66: 299-317.
36. Hacioğlu C, Fatih K, Senturk H, Kanbak G. Neuroprotective effects of boric acid against fluoride toxicity on rat synaptosomes. Med Sci Discov 2018; 5: 260-266.
37. Kızılay Z, Erken HA, Çetin NK, Aktaş S, Abas Bİ, Yılmaz A. Boric acid reduces axonal and myelin damage in experimental sciatic nerve injury. Neural Regen Res 2016; 11: 1660-1665.
38. Aras M, Altas M, Motor S, Dokuyucu R, Yilmaz A, Ozgiray E, et al. Protective effects of minocycline on experimental spinal cord injury in rats. Injury 2015; 46: 1471-1474.
39. Bal E, Hanalioğlu Ş, Apaydın AS, Bal C, Şenat A, Öcal BG, et al. Anti-inflammatory and antioxidative effects of genistein in a model of spinal cord injury in rats. Asian Biomed 2021; 15: 233-243.
40. Yu L, Qian J. Dihydrotanshinone I alleviates spinal cord injury via suppressing inflammatory response, oxidative stress and apoptosis in rats. Med Sci Monit 2020; 26: e920738-920731.
41. Colak S, Geyikoğlu F, Keles ON, Türkez H, Topal A, Unal B. The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity. Toxicol Ind Health 2011; 27: 700-710.
42. Cikler-Dulger E, Sogut I. Investigation of the protective effects of boric acid on ethanol induced kidney injury. Biotech Histochem 2020; 95: 186-193.
43. Balci Yuce H, Toker H, Goze F. The histopathological and morphometric investigation of the effects of systemically administered boric acid on alveolar bone loss in ligature-induced periodontitis in diabetic rats. Acta Odontol Scand 2014; 72: 729-736.
44. Wu KL, Hsu C, Chan JY. Impairment of the mitochondrial respiratory enzyme activity triggers sequential activation of apoptosis‐inducing factor‐dependent and caspase‐dependent signaling pathways to induce apoptosis after spinal cord injury. J Neurochem 2007; 101:1552-1566.
45. Li Q, Gao S, Kang Z, Zhang M, Zhao X, Zhai Y, et al. Rapamycin enhances mitophagy and attenuates apoptosis after spinal ischemia-reperfusion injury. Front Neurosci 2018; 12: 865-874.
46. Springer JE, Azbill RD, Knapp PE. Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Nat Med 1999; 5: 943-946.
47. Yang C-H, Quan Z-X, Wang G-J, He T, Chen Z-Y, Li Q-C, et al. Elevated intraspinal pressure in traumatic spinal cord injury is a promising therapeutic target. Neural Regen Res 2022; 17: 1703-1710.
48. Koc ER, Gökce EC, Sönmez MA, Namuslu M, Gökce A, Bodur AS. Borax partially prevents neurologic disability and oxidative stress in experimental spinal cord ischemia/reperfusion injury. J Stroke Cerebrovasc Dis 2015; 24: 83-90.
49. Cong L, Chen W. Neuroprotective effect of ginsenoside Rd in spinal cord injury rats. Basic Clin Pharmacol Toxicol 2016; 119: 193-201.
Iranian Journal of Basic Medical Sciences
Volume 28, Issue 4
April 2025
Pages 444-450

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