Research Article
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Neuroprotective effect of Hesperidin on experimental spinal cord injury in rats

Year 2022, Volume: 15 Issue: 3, 451 - 459, 01.07.2022

Hasan Ali Aydin Emrah Keskin

https://doi.org/10.31362/patd.1057660

Abstract

Purpose: In this study, we aimed to investigate the protective effect of different doses of Hesperidin (HSP) against oxidative damage in experimental spinal cord injury in rats using histopathological and biochemical evaluations.
Material and Methods: The study was planned as four groups and 10 Wistar albino rats in each group. Group 1 (control group): laminectomy was performed. Trauma was applied to three groups (G2, G3, G4) after laminectomy. Group 2 (pathology group): laminectomy was performed, and an extradural clip was applied. Group 3 (low dose HSP): laminectomy was performed, an extradural clip was applied, and a single low dose HSP was administered intraperitoneally (50 mg/kg). Group 4 (high-dose HSP): laminectomy was performed, an extradural clip was applied, and a single high-dose HSP was administered intraperitoneally (100 mg/kg). Tissue samples taken to evaluate the neuroprotective effect were examined biochemical and histopathological.
Results: Morphometric results of inflammatory findings and neuron number in the trauma groups were significantly better in Group 4 than in the other groups. There was no difference between the groups regarding clinical motor examination and inclined plane test results. Malondialdehyde, the end product of lipid peroxidation, did not differ significantly in both treatment groups (Group3, Group4) (p>0.05); A statistically significant difference was observed in total antioxidant plasma levels compared to the control and pathology groups (p:0.001).
Conclusion: Our results suggest that high-dose HSP may provide a neuroprotective effect with its positive impact on decreasing the number of neurons in spinal cord damage and mild degeneration findings.

Keywords

Hesperidin spinal cord injury neuroprotective effect

References

  • 1. Hachem LD, Ahuja CS, Fehlings MG. Assessment and management of acute spinal cord injury: From point of injury to rehabilitation. Spinal Cord Med 2017;40:665-675. https://doi.org/10.1080/10790268.2017.1329076
  • 2. Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 2001;26:2-12. https://doi.org/10.1097/00007632-200112151-00002
  • 3. Katoh H, Yokota K, Fehlings MG. Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds. Front Cell Neurosci 2019;13:248. https://doi.org/10.3389/fncel.2019.00248
  • 4. Dimitrijevic MR, Danner SM, Mayr W. Neurocontrol of movement in humans with spinal cord injury. Artif. Organs 2017;39:823–833. https://doi.org/10.1111/aor.12614
  • 5. Hall ED, Wolf DL. A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia. J Neurosurg 1986;64:951-961. https://doi.org/10.3171/jns.1986.64.6.0951
  • 6. Stavric B. Role of chemopreventers in human diet. Clin Biochem 1994;27:319-332. https://doi.org/10.1016/0009-9120(94)00039-5
  • 7. Rashid MI, Fareed MI, Rashid H, et al. A Flavonoids and Their Biological Secrets. Plant and Human Health 2019;23:579–605. https://doi.org/10.1007/978-3-030-03344-6_24
  • 8. Hirata A, Murakami Y, Shoji M, et al. Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression. Anticancer Res 2005;25:3367-3374. 9. No Nones J, E Spohr TC, Gomes FC. Hesperidin, a flavone glycoside, as mediator of neuronal survival. Neurochem Res 2011;36:1776-1784. https://doi.org/10.1007/s11064-011-0493-3
  • 10. Hajialyani M, Hosein Farzaei M, Echeverría J, et al. Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence. Molecules 2019;24:648. https://doi.org/10.3390/molecules24030648
  • 11. Rivlin AS, Tator CH. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol 1978;10:38-43.
  • 12. Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol 2008;209:378-388. https://doi.org/10.1016/j.expneurol.2007.06.009
  • 13. Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991;75:15-26. https://doi.org/10.3171/jns.1991.75.1.0015
  • 14. Young W. Spinal cord contusion models. Prog Brain Res. 2002; 137: 231-255. https://doi.org/10.1016/s0079-6123(02)37019-5
  • 15. Kang Y, Ding H, Zhou H, et al. Epidemiology of worldwide spinal cord injury: a literature review. J Neuro-Oncol 2018;6:1–9. https://doi.org/10.2147/JN.S14323610.1016/s0079-6123(02)37019-5
  • 16. Sengul G, Coban MK, Cakir M, et al. Neuroprotective effect of acute interferon-beta 1B treatment after spinal cord injury. Turk Neurosurg 2013;23:45-49. https://doi.org/10.5137/1019-5149.JTN.6651-12.1
  • 17. Zhang P, Hölscher C, Ma X. Therapeutic potential of flavonoids in spinal cord injury. Rev Neurosci 2017;28:87-101. https://doi.org/10.1515/revneuro-2016-0053
  • 18. Hurlbert RJ. Methylprednisolone for the treatment of acute spinal cord injury: point. Neurosurgery 2014;61:32-35. https://doi.org/10.1227/NEU.0000000000000393
  • 19. Walters BC, Hadley MN, Hurlbert RJ, et al. Guidelines for the management of acute cervical spine and spinal cord injuries:2013update. Neurosurgery 2013;60:82-91. https://doi.org/10.1227/01.neu.0000430319.32247.7f
  • 20. Emrah K, Özlem E, Havva Hande KŞ, Berrak G. Efficacy of Annona muricata (graviola) in experimental spinal cord injury: biochemical and histopathological analysis. Ulus Travma Acil Cerrahi Derg, 2022. Doi: 10.14744/tjtes.2021.70728
  • 21. Zhao R, Wu X, Bi XY, et al. Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury. Neural Regen Res 2022;17:1080-1087. https://doi.org/10.4103/1673-5374.324857
  • 22. Metodiewa D, Kochman A, Karolczak S, et al. Evidence for antiradical and antioxidant properties of four biologically active N, N-diethylaminoethyl ethers of flavanone oximes: a comparison with natural polyphenolic flavonoid (rutin) action. Biochem Mol Biol Int 1997;41:1067-1075. https://doi.org/10.1080/15216549700202141
  • 23. Iglesias DJ, Cercos M, Colmenero-Flores, et al. Physiology of citrus fruiting. Brazil J Plant Physiol 2007;19:333-362. https://doi.org/10.1590/S1677-04202007000400006
  • 24. Loguercio C, D'Argenio G, Delle cave M, et al. Direct evidence of oxidative damage in acute and chronic phases of experimental colitis in rats. Dig Dis Sci 1996;41:1204-1211. https://doi.org/10.1007/BF02088238
  • 25. Galati EM, Monforte MT, Kirjavainen S, et al. Biological effects of hesperidin, a citrus flavonoid. (Note I): antiinflammatory and analgesic activity. Farmaco 1994;40:709-712.
  • 26. Tamilselvam K, Braidy N, Manivasagam T, et al. Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson's disease. Oxid Med Cell Longev 2013;2013:102741. https://doi.org/10.1155/2013/102741
  • 27. Ashley NT, Weil ZM, Nelson RJ. Inflammation: mechanisms, costs, and natural variation. Annual Review of Ecology, Evolution, and Systematics 2012;43:385-406. https://doi.org/10.1146/annurev-ecolsys-040212-092530
  • 28. Bareyre FM, Schwab ME. Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci 2003;26:555-563. https://doi.org/10.1016/j.tins.2003.08.004
  • 29. Toborek M, Malecki A, Garrido R, et al. Arachidonic acid-induced oxidative injury to cultured spinal cord neurons. J Neurochem 1999;73:684-692. https://doi.org/10.1046/j.1471-4159.1999.0730684.x
  • 30. Barut S, Canbolat A, Bilge T, et al. Lipid peroxidation in experimental spinal cord injury: time-level relationship. Neurosurg Rev 1993;16:53-59. https://doi.org/10.1007/BF00308614
  • 31. Ren XS, Ding W, Yang XY. [Neuroprotective effect of icariin on spinal cord injury in rats]. Zhongguo Gu Shang 2018;31:1054-1060. https://doi.org/10.3969/j.issn.1003-0034.2018.11.014
  • 32. Wang Y, Li W, Wang M, et al. Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats. J Cell Biochem 2018;119:2298-2306. https://doi.org/10.1002/jcb.26392
  • 33. Kandhare AD, Shivakumar V, Rajmane A, et al. Evaluation of the neuroprotective effect of chrysin via modulation of endogenous biomarkers in a rat model of spinal cord injury. J Nat Med 2014;68:586-603. https://doi.org/10.1007/s11418-014-0840-1
  • 34. Oztanir MN, Ciftci O, Cetin A, et al. Hesperidin attenuates oxidative and neuronal damage caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model. Neurol Sci 2014;35:1393-1399. https://doi.org/10.1007/s10072-014-1725-5
  • 35. Kamisli S, Ciftci O, Kaya K, et al. Hesperidin protects brain and sciatic nerve tissues against cisplatin-induced oxidative, histological and electromyographical side effects in rats. Toxicol Ind Health 2015;31:841-851. https://doi.org/10.1177/0748233713483192
  • 36. Heo SD, Kim J, Choi Y, et al. Hesperidin improves motor disability in rat spinal cord injury through anti-inflammatory and antioxidant mechanism via Nrf-2/HO-1 pathway. Neurosci Lett 2020;715:134619. https://doi.org/10.1016/j.neulet.2019.134619
  • 37. Yurtal Z, Altug ME, Unsaldi E, et al. Investigation of Neuroprotective and Therapeutic Effects of Hesperidin in Experimental Spinal Cord Injury. Turk Neurosurg 2020;30:899-906. https://doi.org/10.5137/1019-5149.JTN.29611-20.2

Ratlarda deneysel spinal kord yaralanmasında Hesperidin’in nöroprotektif etkisi

Year 2022, Volume: 15 Issue: 3, 451 - 459, 01.07.2022

Hasan Ali Aydin Emrah Keskin

https://doi.org/10.31362/patd.1057660

Abstract

Amaç: Bu çalışmada, ratlarda deneysel omurilik yaralanmasında farklı dozlarda hesperidinin (HSP) oksidatif hasara karşı koruyucu etkisini histopatolojik ve biyokimyasal değerlendirmeler kullanarak araştırmayı amaçladık.
Gereç ve yöntem: Çalışma 4 grup ve her grupta 10 adet Wistar albino cinsi rat olacak şekilde planlandı. Grup 1 (kontrol grubu): laminektomi yapıldı. Laminektomi sonrası üç gruba (G2, G3, G4) travma uygulandı. Grup 2 (patoloji grubu): laminektomi yapıldı ve ekstradural klip uygulandı. Grup 3 (düşük doz HSP): laminektomi yapılıp, ekstradural klip uygulandı ve tek doz düşük doz HSP intraperitoneal olarak verildi (50 mg/kg). Grup 4 (yüksek doz HSP): laminektomi yapılıp, ekstradural klip uygulandı ve tek doz yüksek doz HSP intraperitoneal olarak verildi (100 mg/kg). Nöroprotektif etkiyi değerlendirmek için alınan doku örnekleri biyokimyasal ve histopatolojik olarak incelendi.
Bulgular: Travma gruplarındaki inflamatuar bulgular ve nöron sayısının morfometrik sonuçları, Grup 4‘te diğer gruplara kıyasla istatiksel olarak anlamlı şekilde daha iyiydi. Klinik motor muayene ve eğik düzlem test sonuçları açısından gruplar arasında fark yoktu. Her iki tedavi grubunda (Grup3, Grup4), lipid peroksidasyonunun son ürünü olan malondialdehit anlamlı bir farklılık gözlemlenmezken (p>0,05); total antioksidan plazma seviyelerinde kontrol ve patoloji gruplarına kıyasla istatistiksel olarak anlamlı bir farklılık gözlemlendi (p:0,001).
Sonuç: Sonuçlarımız, yüksek doz HSP’ nin spinal kord hasarında nöronların sayısındaki azalmaya olumlu etkisi ve hafif dejenerasyon bulguları ile neuroprotektif etki sağlayabileceğini düşündürmektedir.

Keywords

Hesperidin spinal kord yaralanma neuroprotektif etki

References

  • 1. Hachem LD, Ahuja CS, Fehlings MG. Assessment and management of acute spinal cord injury: From point of injury to rehabilitation. Spinal Cord Med 2017;40:665-675. https://doi.org/10.1080/10790268.2017.1329076
  • 2. Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine 2001;26:2-12. https://doi.org/10.1097/00007632-200112151-00002
  • 3. Katoh H, Yokota K, Fehlings MG. Regeneration of Spinal Cord Connectivity Through Stem Cell Transplantation and Biomaterial Scaffolds. Front Cell Neurosci 2019;13:248. https://doi.org/10.3389/fncel.2019.00248
  • 4. Dimitrijevic MR, Danner SM, Mayr W. Neurocontrol of movement in humans with spinal cord injury. Artif. Organs 2017;39:823–833. https://doi.org/10.1111/aor.12614
  • 5. Hall ED, Wolf DL. A pharmacological analysis of the pathophysiological mechanisms of posttraumatic spinal cord ischemia. J Neurosurg 1986;64:951-961. https://doi.org/10.3171/jns.1986.64.6.0951
  • 6. Stavric B. Role of chemopreventers in human diet. Clin Biochem 1994;27:319-332. https://doi.org/10.1016/0009-9120(94)00039-5
  • 7. Rashid MI, Fareed MI, Rashid H, et al. A Flavonoids and Their Biological Secrets. Plant and Human Health 2019;23:579–605. https://doi.org/10.1007/978-3-030-03344-6_24
  • 8. Hirata A, Murakami Y, Shoji M, et al. Kinetics of radical-scavenging activity of hesperetin and hesperidin and their inhibitory activity on COX-2 expression. Anticancer Res 2005;25:3367-3374. 9. No Nones J, E Spohr TC, Gomes FC. Hesperidin, a flavone glycoside, as mediator of neuronal survival. Neurochem Res 2011;36:1776-1784. https://doi.org/10.1007/s11064-011-0493-3
  • 10. Hajialyani M, Hosein Farzaei M, Echeverría J, et al. Hesperidin as a Neuroprotective Agent: A Review of Animal and Clinical Evidence. Molecules 2019;24:648. https://doi.org/10.3390/molecules24030648
  • 11. Rivlin AS, Tator CH. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surg Neurol 1978;10:38-43.
  • 12. Donnelly DJ, Popovich PG. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol 2008;209:378-388. https://doi.org/10.1016/j.expneurol.2007.06.009
  • 13. Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 1991;75:15-26. https://doi.org/10.3171/jns.1991.75.1.0015
  • 14. Young W. Spinal cord contusion models. Prog Brain Res. 2002; 137: 231-255. https://doi.org/10.1016/s0079-6123(02)37019-5
  • 15. Kang Y, Ding H, Zhou H, et al. Epidemiology of worldwide spinal cord injury: a literature review. J Neuro-Oncol 2018;6:1–9. https://doi.org/10.2147/JN.S14323610.1016/s0079-6123(02)37019-5
  • 16. Sengul G, Coban MK, Cakir M, et al. Neuroprotective effect of acute interferon-beta 1B treatment after spinal cord injury. Turk Neurosurg 2013;23:45-49. https://doi.org/10.5137/1019-5149.JTN.6651-12.1
  • 17. Zhang P, Hölscher C, Ma X. Therapeutic potential of flavonoids in spinal cord injury. Rev Neurosci 2017;28:87-101. https://doi.org/10.1515/revneuro-2016-0053
  • 18. Hurlbert RJ. Methylprednisolone for the treatment of acute spinal cord injury: point. Neurosurgery 2014;61:32-35. https://doi.org/10.1227/NEU.0000000000000393
  • 19. Walters BC, Hadley MN, Hurlbert RJ, et al. Guidelines for the management of acute cervical spine and spinal cord injuries:2013update. Neurosurgery 2013;60:82-91. https://doi.org/10.1227/01.neu.0000430319.32247.7f
  • 20. Emrah K, Özlem E, Havva Hande KŞ, Berrak G. Efficacy of Annona muricata (graviola) in experimental spinal cord injury: biochemical and histopathological analysis. Ulus Travma Acil Cerrahi Derg, 2022. Doi: 10.14744/tjtes.2021.70728
  • 21. Zhao R, Wu X, Bi XY, et al. Baicalin attenuates blood-spinal cord barrier disruption and apoptosis through PI3K/Akt signaling pathway after spinal cord injury. Neural Regen Res 2022;17:1080-1087. https://doi.org/10.4103/1673-5374.324857
  • 22. Metodiewa D, Kochman A, Karolczak S, et al. Evidence for antiradical and antioxidant properties of four biologically active N, N-diethylaminoethyl ethers of flavanone oximes: a comparison with natural polyphenolic flavonoid (rutin) action. Biochem Mol Biol Int 1997;41:1067-1075. https://doi.org/10.1080/15216549700202141
  • 23. Iglesias DJ, Cercos M, Colmenero-Flores, et al. Physiology of citrus fruiting. Brazil J Plant Physiol 2007;19:333-362. https://doi.org/10.1590/S1677-04202007000400006
  • 24. Loguercio C, D'Argenio G, Delle cave M, et al. Direct evidence of oxidative damage in acute and chronic phases of experimental colitis in rats. Dig Dis Sci 1996;41:1204-1211. https://doi.org/10.1007/BF02088238
  • 25. Galati EM, Monforte MT, Kirjavainen S, et al. Biological effects of hesperidin, a citrus flavonoid. (Note I): antiinflammatory and analgesic activity. Farmaco 1994;40:709-712.
  • 26. Tamilselvam K, Braidy N, Manivasagam T, et al. Neuroprotective effects of hesperidin, a plant flavanone, on rotenone-induced oxidative stress and apoptosis in a cellular model for Parkinson's disease. Oxid Med Cell Longev 2013;2013:102741. https://doi.org/10.1155/2013/102741
  • 27. Ashley NT, Weil ZM, Nelson RJ. Inflammation: mechanisms, costs, and natural variation. Annual Review of Ecology, Evolution, and Systematics 2012;43:385-406. https://doi.org/10.1146/annurev-ecolsys-040212-092530
  • 28. Bareyre FM, Schwab ME. Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci 2003;26:555-563. https://doi.org/10.1016/j.tins.2003.08.004
  • 29. Toborek M, Malecki A, Garrido R, et al. Arachidonic acid-induced oxidative injury to cultured spinal cord neurons. J Neurochem 1999;73:684-692. https://doi.org/10.1046/j.1471-4159.1999.0730684.x
  • 30. Barut S, Canbolat A, Bilge T, et al. Lipid peroxidation in experimental spinal cord injury: time-level relationship. Neurosurg Rev 1993;16:53-59. https://doi.org/10.1007/BF00308614
  • 31. Ren XS, Ding W, Yang XY. [Neuroprotective effect of icariin on spinal cord injury in rats]. Zhongguo Gu Shang 2018;31:1054-1060. https://doi.org/10.3969/j.issn.1003-0034.2018.11.014
  • 32. Wang Y, Li W, Wang M, et al. Quercetin reduces neural tissue damage and promotes astrocyte activation after spinal cord injury in rats. J Cell Biochem 2018;119:2298-2306. https://doi.org/10.1002/jcb.26392
  • 33. Kandhare AD, Shivakumar V, Rajmane A, et al. Evaluation of the neuroprotective effect of chrysin via modulation of endogenous biomarkers in a rat model of spinal cord injury. J Nat Med 2014;68:586-603. https://doi.org/10.1007/s11418-014-0840-1
  • 34. Oztanir MN, Ciftci O, Cetin A, et al. Hesperidin attenuates oxidative and neuronal damage caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model. Neurol Sci 2014;35:1393-1399. https://doi.org/10.1007/s10072-014-1725-5
  • 35. Kamisli S, Ciftci O, Kaya K, et al. Hesperidin protects brain and sciatic nerve tissues against cisplatin-induced oxidative, histological and electromyographical side effects in rats. Toxicol Ind Health 2015;31:841-851. https://doi.org/10.1177/0748233713483192
  • 36. Heo SD, Kim J, Choi Y, et al. Hesperidin improves motor disability in rat spinal cord injury through anti-inflammatory and antioxidant mechanism via Nrf-2/HO-1 pathway. Neurosci Lett 2020;715:134619. https://doi.org/10.1016/j.neulet.2019.134619
  • 37. Yurtal Z, Altug ME, Unsaldi E, et al. Investigation of Neuroprotective and Therapeutic Effects of Hesperidin in Experimental Spinal Cord Injury. Turk Neurosurg 2020;30:899-906. https://doi.org/10.5137/1019-5149.JTN.29611-20.2
There are 36 citations in total.

Details

Primary Language Turkish
Subjects Surgery
Journal Section Research Article
Authors

Hasan Ali Aydin 0000-0002-0883-4611

Emrah Keskin 0000-0001-5326-741X

Publication Date July 1, 2022
Submission Date January 14, 2022
Acceptance Date February 2, 2022
Published in Issue Year 2022 Volume: 15 Issue: 3

Cite

APA Aydin, H. A., & Keskin, E. (2022). Ratlarda deneysel spinal kord yaralanmasında Hesperidin’in nöroprotektif etkisi. Pamukkale Medical Journal, 15(3), 451-459. https://doi.org/10.31362/patd.1057660
AMA Aydin HA, Keskin E. Ratlarda deneysel spinal kord yaralanmasında Hesperidin’in nöroprotektif etkisi. Pam Med J. July 2022;15(3):451-459. doi:10.31362/patd.1057660
Chicago Aydin, Hasan Ali, and Emrah Keskin. “Ratlarda Deneysel Spinal Kord yaralanmasında Hesperidin’in nöroprotektif Etkisi”. Pamukkale Medical Journal 15, no. 3 (July 2022): 451-59. https://doi.org/10.31362/patd.1057660.
EndNote Aydin HA, Keskin E (July 1, 2022) Ratlarda deneysel spinal kord yaralanmasında Hesperidin’in nöroprotektif etkisi. Pamukkale Medical Journal 15 3 451–459.
IEEE H. A. Aydin and E. Keskin, “Ratlarda deneysel spinal kord yaralanmasında Hesperidin’in nöroprotektif etkisi”, Pam Med J, vol. 15, no. 3, pp. 451–459, 2022, doi: 10.31362/patd.1057660.
ISNAD Aydin, Hasan Ali - Keskin, Emrah. “Ratlarda Deneysel Spinal Kord yaralanmasında Hesperidin’in nöroprotektif Etkisi”. Pamukkale Medical Journal 15/3 (July 2022), 451-459. https://doi.org/10.31362/patd.1057660.
JAMA Aydin HA, Keskin E. Ratlarda deneysel spinal kord yaralanmasında Hesperidin’in nöroprotektif etkisi. Pam Med J. 2022;15:451–459.
MLA Aydin, Hasan Ali and Emrah Keskin. “Ratlarda Deneysel Spinal Kord yaralanmasında Hesperidin’in nöroprotektif Etkisi”. Pamukkale Medical Journal, vol. 15, no. 3, 2022, pp. 451-9, doi:10.31362/patd.1057660.
Vancouver Aydin HA, Keskin E. Ratlarda deneysel spinal kord yaralanmasında Hesperidin’in nöroprotektif etkisi. Pam Med J. 2022;15(3):451-9.

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