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Troloks ve Neokuproin’in Sıçanlarda Deneysel Hafif Travma Sonucu Beyin Hasarı Üzerindeki Terapötik Etkisi

Year 2024, Volume: 26 Issue: 3, 263 - 268, 30.12.2024
https://doi.org/10.18678/dtfd.1562334

Abstract

Amaç: Bu çalışmanın amacı hafif travmatik beyin hasarı (hTBH) olan deneysel rat modelinde Troloks ve neokuprin tedavilerinin terapötik etkinliğinin değerlendirilmesidir.
Gereç ve Yöntemler: Kırk rat, kontrol, TBH, Troloks ve neokuprin olarak gruplandırıldı. TBH oluşturmak amacı ile Marmarou Weight Drop Model uygulandıktan sonraki 2. saat diliminde 80 mg/kg/gün Troloks (i.p.) ve 100 μM/gün neokuproin (i.p.) tedavileri yapıldı. Lokomotor aktiviteyi ölçmek için açık alan ve dikkat ve kısa süreli hafıza yeni nesne tanıma testleri gerçekleştirildi. Sıçanların hipokampüs dokularındaki IL-1β, IL-10, TNF-α ve TGF-β düzeyleri ELISA yöntemi ile analiz edildi.
Bulgular: Açık alan ve yeni nesne tanıma test sonuçları, alınan toplam yolun TBH grubunda kontrol grubuna kıyasla önemli ölçüde azaldığını gösterdi (p<0,001). Troloks (p=0,018) ve neokuproin (p=0,002) gruplarında ise TBH’a kıyasla lokomotor fonksiyonlarında anlamlı bir artış gözlendi. Kısa süreli bellek test sonuçları, TBH’da kontrole kıyasla azalırken (p<0,001), Troloks ve neokuproin gruplarında ise TBH’a kıyasla arttı (her iki p<0,001). Kontrole kıyasla TBH grubunun hipokampüs IL-1β (p=0,012) ve TNF-α (p=0,011) seviyeleri artarken, IL-10 (p=0,031) ve TGF-β (p=0,007) seviyeleri azaldı. Troloks ve neokuproin gruplarında TBH’ye kıyasla tüm proinflamatuar sitokin seviyeleri azalırken, antiinflamatuar sitokin seviyeleri arttı.
Sonuç: Elde edilen bulgular, TBH’da Troloks ve neokuproin tedavilerinin proinflamatuar sitokin üretimini azaltarak ve antiinflamatuar sitokin üretimini artırarak kısa süreli bellek ve lokomotor aktivite düzeyinde anlamlı iyileşmeler sağladıklarını göstermiştir.

References

  • Pop V, Badaut J. A neurovascular perspective for long-term changes after brain trauma. Transl Stroke Res. 2011;2(4):533-45.
  • Akçay G. Weight drop models in traumatic brain injury. Mid Blac Sea J Health Sci. 2023;9(2):375-84.
  • Yi JH, Hazell AS. Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem Int. 2006;48(5):394-403.
  • Akçay G, Baydemir R. Therapeutic effects of transcranial direct current stimulation on loss of motor function caused by experimental mild traumatic brain injury. Cukurova Med J. 2023;48(3):972-8.
  • Ricciarelli R, Azzi A, Zingg JM. Reduction of senescence-associated beta-galactosidase activity by vitamin E in human fibroblasts depends on subjects' age and cell passage number. Biofactors. 2020;46(4):665-74.
  • Göçmen C, Giesselman B, de Groat WC. Effect of neocuproine, a copper(i) chelator, on rat bladder function. J Pharmacol Exp Ther. 2005;312(3):1138-43.
  • De Man JG, Moreels TG, De Winter BY, Herman AG, Pelckmans PA. Neocuproine potentiates the activity of the nitrergic neurotransmitter but inhibits that of S-nitrosothiols. Eur J Pharmacol. 1999;24;381(2-3):151-9.
  • Viviani B, Corsini E, Binaglia M, Galli CL, Marinovich M. Reactive oxygen species generated by glia are responsible for neuron death induced by human immunodeficiency virus-glycoprotein 120 in vitro. Neuroscience. 2001;107(1):51-8.
  • Brunetti L, Orlando G, Michelotto B, Recinella L, Di Nisio C, Ciabattoni G, et al. Identification of 8-iso-prostaglandin F(2alpha) in rat brain neuronal endings: a possible marker of membrane phospholipid peroxidation. Life Sci. 2002;71(20):2447-55.
  • Göçmen C, Göktürk HS, Ertuğ PU, Onder S, Dikmen A, Baysal F. Effect of neocuproine, a selective Cu(I) chelator, on nitrergic relaxations in the mouse corpus cavernosum. Eur J Pharmacol. 2000;406(2):293-300.
  • Applebaum YJ, Kuvin J, Borman JB, Uretzky G, Chevion M. The protective role of neocuproine against cardiac damage in isolated perfused rat hearts. Free Radic Biol Med. 1990;8(2):133-43.
  • Takahashi K, Takita T, Umezawa H. Effects of o-phenanthroline, 2,2'-dipyridyl and neocuproine on the activities of bleomycin to inhibit DNA synthesis and growth of cultured cells. J Antibiot (Tokyo). 1986;39(10):1473-8.
  • Jahani S, Noroozifar M, Khorasani-Motlagh M, Torkzadeh-Mahani M, Adeli-Sardou M. In vitro cytotoxicity studies of parent and nanoencapsulated Holmium-2,9-dimethyl-1,10-phenanthroline complex toward fish-salmon DNA-binding properties and antibacterial activity. J Biomol Struct Dyn. 2019;37(17):4437-49.
  • Nunes EA, Manieri TM, Matias AC, Bertuchi FR, da Silva DA, Lago L, et al. Protective effects of neocuproine copper chelator against oxidative damage in NSC34 cells. Mutat Res Genet Toxicol Environ Mutagen. 2018;836(Pt B):62-71.
  • Sharma SS, Kaundal RK. Neuroprotective effects of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), an antioxidant in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Neurol Res. 2007;29(3):304-9.
  • Park H, Seol GH, Ryu S, Choi IY. Neuroprotective effects of (-)-linalool against oxygen-glucose deprivation-induced neuronal injury. Arch Pharm Res. 2016;39(4):555-64.
  • Massaeli H, Sobrattee S, Pierce GN. The importance of lipid solubility in antioxidants and free radical generating systems for determining lipoprotein proxidation. Free Radic Biol Med. 1999;26(11-12):1524-30.
  • Akcay G, Demirdogen F, Gul T, Yilmaz A, Kotan D, Karakoc E, et al. Effects of transcranial direct current stimulation on motor and cognitive dysfunction in an experimental traumatic brain injury model. Turk Neurosurg. 2024;34(2):343-50.
  • Akcay G, Ozdemir F, Ozkinali S, Demirdogen F, Yilmaz A, Celik C. Investigation of the protective and therapeutic effects of ginger (Zingiber officinale) extracts on neuroinflammatory, motor and cognitive impairments caused by mild traumatic brain injury model. Turk Neurosurg. 2024;[Epub ahead of print]. doi: 10.5137/1019-5149.JTN.46057-23.7
  • Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H. Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg. 1994;80(2):291-300.
  • Berry A, Tomidokoro Y, Ghiso J, Thornton J. Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-beta levels in female rats. Horm Behav. 2008;54(1):143-52.
  • Denenberg VH. Open-field bheavior in the rat: what does it mean? Ann N Y Acad Sci. 1969;159(3):852-9.
  • Johnston IN, Tan M, Cao J, Matsos A, Forrest DRL, Si E, et al. MR. Ibudilast reduces oxaliplatin-induced tactile allodynia and cognitive impairments in rats. Behav Brain Res. 2017;334:109-18.
  • Galgano M, Toshkezi G, Qiu X, Russell T, Chin L, Zhao LR. Traumatic brain injury: current treatment strategies and future endeavors. Cell Transplant. 2017;26(7):1118-30.
  • Yang B, Zhang R, Sa Q, Du Y. Rhamnazin ameliorates traumatic brain injury in mice via reduction in apoptosis, oxidative stress, and inflammation. Neuroimmunomodulation. 2022;29(1):28-35.
  • Thompson FJ, Hou J, Bose PK. Closed-head TBI model of multiple morbidity. Methods Mol Biol. 2016;1462:521-36.
  • Xing P, Ma K, Li L, Wang D, Hu G, Long W. The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury. Acta Cir Bras. 2018;33(4):341-53.
  • Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic brain injury: An overview of epidemiology, pathophysiology, and medical management. Med Clin North Am. 2020;104(2):213-38.
  • Ma X, Aravind A, Pfister BJ, Chandra N, Haorah J. Animal models of traumatic brain injury and assessment of injury severity. Mol Neurobiol. 2019;56(8):5332-45.
  • Kurniawan VR, Islam AA, Adhimarta W, Zainuddin AA, Widodo D, Nasrullah, et al. The role of diphenhydramine HCl on tumor necrosis factor-α levels in Wistar rats with traumatic brain injury: An in vivo study. Ann Med Surg (Lond). 2022;81:104399.
  • Bennett ER, Reuter-Rice K, Laskowitz DT. Genetic influences in traumatic brain injury. In: Laskowitz D, Grant G, editors. Translational research in traumatic brain injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Chapter 9.

Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats

Year 2024, Volume: 26 Issue: 3, 263 - 268, 30.12.2024
https://doi.org/10.18678/dtfd.1562334

Abstract

Aim: This study aimed to evaluate the therapeutic efficacy of Trolox and neocuproine treatment in an experimental rat model of mild traumatic brain injury (mTBI).
Material and Methods: Forty rats were grouped as Control, TBI, Trolox, and neocuproine. After the Marmarou Weight Drop Model was used to create TBI, 80 mg/kg/day Trolox (i.p.), and 100 μM/day Neocuproine (i.p.) treatments were applied in the 2nd hour. Open field, attention, and short-term memory novel object recognition tests were performed to measure locomotor activity. IL-1β, IL-10, TNF-α, and TGF-β levels in the hippocampus tissues of the rats were analyzed by the ELISA method.
Results: Open field and novel object recognition test results showed that the total path traveled was significantly decreased in the TBI group compared to the control group (p<0.001). A significant increase in locomotor functions was observed in the Trolox (p=0.018) and neocuproine (p=0.002) groups compared to TBI. Short-term memory test results decreased in TBI compared to control (p<0.001), while they increased in the Trolox and neocuproine groups compared to TBI (both p<0.001). Hippocampus IL-1β (p=0.012) and TNF-α (p=0.011) levels increased, while IL-10 (p=0.031) and TGF-β (p=0.007) levels decreased compared to control in the TBI group. While all proinflammatory cytokine levels decreased, antiinflammatory cytokine levels increased in the Trolox and neocuproine groups compared to TBI.
Conclusion: The present findings showed that Trolox and neocuproine treatments in TBI provided significant improvements in short-term memory, and locomotor activity levels by reducing proinflammatory cytokine production, and increasing antiinflammatory cytokine production.

References

  • Pop V, Badaut J. A neurovascular perspective for long-term changes after brain trauma. Transl Stroke Res. 2011;2(4):533-45.
  • Akçay G. Weight drop models in traumatic brain injury. Mid Blac Sea J Health Sci. 2023;9(2):375-84.
  • Yi JH, Hazell AS. Excitotoxic mechanisms and the role of astrocytic glutamate transporters in traumatic brain injury. Neurochem Int. 2006;48(5):394-403.
  • Akçay G, Baydemir R. Therapeutic effects of transcranial direct current stimulation on loss of motor function caused by experimental mild traumatic brain injury. Cukurova Med J. 2023;48(3):972-8.
  • Ricciarelli R, Azzi A, Zingg JM. Reduction of senescence-associated beta-galactosidase activity by vitamin E in human fibroblasts depends on subjects' age and cell passage number. Biofactors. 2020;46(4):665-74.
  • Göçmen C, Giesselman B, de Groat WC. Effect of neocuproine, a copper(i) chelator, on rat bladder function. J Pharmacol Exp Ther. 2005;312(3):1138-43.
  • De Man JG, Moreels TG, De Winter BY, Herman AG, Pelckmans PA. Neocuproine potentiates the activity of the nitrergic neurotransmitter but inhibits that of S-nitrosothiols. Eur J Pharmacol. 1999;24;381(2-3):151-9.
  • Viviani B, Corsini E, Binaglia M, Galli CL, Marinovich M. Reactive oxygen species generated by glia are responsible for neuron death induced by human immunodeficiency virus-glycoprotein 120 in vitro. Neuroscience. 2001;107(1):51-8.
  • Brunetti L, Orlando G, Michelotto B, Recinella L, Di Nisio C, Ciabattoni G, et al. Identification of 8-iso-prostaglandin F(2alpha) in rat brain neuronal endings: a possible marker of membrane phospholipid peroxidation. Life Sci. 2002;71(20):2447-55.
  • Göçmen C, Göktürk HS, Ertuğ PU, Onder S, Dikmen A, Baysal F. Effect of neocuproine, a selective Cu(I) chelator, on nitrergic relaxations in the mouse corpus cavernosum. Eur J Pharmacol. 2000;406(2):293-300.
  • Applebaum YJ, Kuvin J, Borman JB, Uretzky G, Chevion M. The protective role of neocuproine against cardiac damage in isolated perfused rat hearts. Free Radic Biol Med. 1990;8(2):133-43.
  • Takahashi K, Takita T, Umezawa H. Effects of o-phenanthroline, 2,2'-dipyridyl and neocuproine on the activities of bleomycin to inhibit DNA synthesis and growth of cultured cells. J Antibiot (Tokyo). 1986;39(10):1473-8.
  • Jahani S, Noroozifar M, Khorasani-Motlagh M, Torkzadeh-Mahani M, Adeli-Sardou M. In vitro cytotoxicity studies of parent and nanoencapsulated Holmium-2,9-dimethyl-1,10-phenanthroline complex toward fish-salmon DNA-binding properties and antibacterial activity. J Biomol Struct Dyn. 2019;37(17):4437-49.
  • Nunes EA, Manieri TM, Matias AC, Bertuchi FR, da Silva DA, Lago L, et al. Protective effects of neocuproine copper chelator against oxidative damage in NSC34 cells. Mutat Res Genet Toxicol Environ Mutagen. 2018;836(Pt B):62-71.
  • Sharma SS, Kaundal RK. Neuroprotective effects of 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), an antioxidant in middle cerebral artery occlusion induced focal cerebral ischemia in rats. Neurol Res. 2007;29(3):304-9.
  • Park H, Seol GH, Ryu S, Choi IY. Neuroprotective effects of (-)-linalool against oxygen-glucose deprivation-induced neuronal injury. Arch Pharm Res. 2016;39(4):555-64.
  • Massaeli H, Sobrattee S, Pierce GN. The importance of lipid solubility in antioxidants and free radical generating systems for determining lipoprotein proxidation. Free Radic Biol Med. 1999;26(11-12):1524-30.
  • Akcay G, Demirdogen F, Gul T, Yilmaz A, Kotan D, Karakoc E, et al. Effects of transcranial direct current stimulation on motor and cognitive dysfunction in an experimental traumatic brain injury model. Turk Neurosurg. 2024;34(2):343-50.
  • Akcay G, Ozdemir F, Ozkinali S, Demirdogen F, Yilmaz A, Celik C. Investigation of the protective and therapeutic effects of ginger (Zingiber officinale) extracts on neuroinflammatory, motor and cognitive impairments caused by mild traumatic brain injury model. Turk Neurosurg. 2024;[Epub ahead of print]. doi: 10.5137/1019-5149.JTN.46057-23.7
  • Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H. Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg. 1994;80(2):291-300.
  • Berry A, Tomidokoro Y, Ghiso J, Thornton J. Human chorionic gonadotropin (a luteinizing hormone homologue) decreases spatial memory and increases brain amyloid-beta levels in female rats. Horm Behav. 2008;54(1):143-52.
  • Denenberg VH. Open-field bheavior in the rat: what does it mean? Ann N Y Acad Sci. 1969;159(3):852-9.
  • Johnston IN, Tan M, Cao J, Matsos A, Forrest DRL, Si E, et al. MR. Ibudilast reduces oxaliplatin-induced tactile allodynia and cognitive impairments in rats. Behav Brain Res. 2017;334:109-18.
  • Galgano M, Toshkezi G, Qiu X, Russell T, Chin L, Zhao LR. Traumatic brain injury: current treatment strategies and future endeavors. Cell Transplant. 2017;26(7):1118-30.
  • Yang B, Zhang R, Sa Q, Du Y. Rhamnazin ameliorates traumatic brain injury in mice via reduction in apoptosis, oxidative stress, and inflammation. Neuroimmunomodulation. 2022;29(1):28-35.
  • Thompson FJ, Hou J, Bose PK. Closed-head TBI model of multiple morbidity. Methods Mol Biol. 2016;1462:521-36.
  • Xing P, Ma K, Li L, Wang D, Hu G, Long W. The protection effect and mechanism of hyperbaric oxygen therapy in rat brain with traumatic injury. Acta Cir Bras. 2018;33(4):341-53.
  • Capizzi A, Woo J, Verduzco-Gutierrez M. Traumatic brain injury: An overview of epidemiology, pathophysiology, and medical management. Med Clin North Am. 2020;104(2):213-38.
  • Ma X, Aravind A, Pfister BJ, Chandra N, Haorah J. Animal models of traumatic brain injury and assessment of injury severity. Mol Neurobiol. 2019;56(8):5332-45.
  • Kurniawan VR, Islam AA, Adhimarta W, Zainuddin AA, Widodo D, Nasrullah, et al. The role of diphenhydramine HCl on tumor necrosis factor-α levels in Wistar rats with traumatic brain injury: An in vivo study. Ann Med Surg (Lond). 2022;81:104399.
  • Bennett ER, Reuter-Rice K, Laskowitz DT. Genetic influences in traumatic brain injury. In: Laskowitz D, Grant G, editors. Translational research in traumatic brain injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Chapter 9.
There are 31 citations in total.

Details

Primary Language English
Subjects Central Nervous System, Neurology and Neuromuscular Diseases
Journal Section Research Article
Authors

Selma Yaman 0000-0002-9301-9119

Güven Akçay 0000-0003-3418-8825

Fatma Yesilyurt 0000-0002-1336-6322

Early Pub Date December 20, 2024
Publication Date December 30, 2024
Submission Date October 7, 2024
Acceptance Date December 13, 2024
Published in Issue Year 2024 Volume: 26 Issue: 3

Cite

APA Yaman, S., Akçay, G., & Yesilyurt, F. (2024). Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats. Duzce Medical Journal, 26(3), 263-268. https://doi.org/10.18678/dtfd.1562334
AMA Yaman S, Akçay G, Yesilyurt F. Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats. Duzce Med J. December 2024;26(3):263-268. doi:10.18678/dtfd.1562334
Chicago Yaman, Selma, Güven Akçay, and Fatma Yesilyurt. “Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats”. Duzce Medical Journal 26, no. 3 (December 2024): 263-68. https://doi.org/10.18678/dtfd.1562334.
EndNote Yaman S, Akçay G, Yesilyurt F (December 1, 2024) Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats. Duzce Medical Journal 26 3 263–268.
IEEE S. Yaman, G. Akçay, and F. Yesilyurt, “Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats”, Duzce Med J, vol. 26, no. 3, pp. 263–268, 2024, doi: 10.18678/dtfd.1562334.
ISNAD Yaman, Selma et al. “Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats”. Duzce Medical Journal 26/3 (December 2024), 263-268. https://doi.org/10.18678/dtfd.1562334.
JAMA Yaman S, Akçay G, Yesilyurt F. Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats. Duzce Med J. 2024;26:263–268.
MLA Yaman, Selma et al. “Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats”. Duzce Medical Journal, vol. 26, no. 3, 2024, pp. 263-8, doi:10.18678/dtfd.1562334.
Vancouver Yaman S, Akçay G, Yesilyurt F. Therapeutic Effects of Trolox and Neocuproine on Experimental Mild Traumatic Brain Injury in Rats. Duzce Med J. 2024;26(3):263-8.