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Akut Karbonmonoksit İntoksikasyonunda Deksmedetomidin’in Nöroprotektif Etkileri: Deneysel Bir Çalışma

Year 2025, Volume: 7 Issue: 1, 20 - 28, 25.02.2025
https://doi.org/10.52827/hititmedj.1485232

Abstract

Amaç: Antioksidan, antiapopitotik, antiinflamatuar özellikleri olan Deksmedetomidin’in (DEX) akut karbonmonoksit (CO) toksikasyonunda nöroprotektif etkilerinin değerlendirmesi amaçlanmıştır.
Gereç ve Yöntem: 28 adet Wistar-Albino dişi sıçan kontrol, CO zehirlenme, CO zehirlenme + DEX ve sadece DEX olmak üzere rastgele dört gruba ayrıldı. Çalışma gruplarındaki sıçanlar 3000 ppm konsantrasyonda CO’e 30 dakika boyunca maruz bırakıldı. DEX CO maruziyetinden yarım saat sonra uygulandı. Deney bitiminde sakrifiye edilen sıçanlardan kan ve doku örnekleri alındı. Prefrontal ve hipokampal alanlardan alınan doku örneklerinde Bcl-2 İmmunopositif hücre değerleri immunohistokimyasal yöntem ile elde edilen Bcl-2 antikorların immune ekspresyonlarının ışık mikroskobu altında incelenmesi ile skorlandı. Alınan kan ve sağ hemisfer beyin doku örneklerinden biyokimyasal yöntemlerle malondialdehit (MDA), nitrik oksit (NO), asimetrik dimetilarjinin (ADMA) düzeyleri ile süperoksit düsmutaz (SOD) ve katalaz (CAT) aktivite değerleri ölçüldü.
Bulgular: Deney grupları arasında CAT, SOD, MDA, ADMA ve NO değerleri istatistiksel olarak farklı idi (p<0,001). Post-hoc ikişerli karşılaştırma test sonuçlarına göre yalnız DEX grubu ve kontrol grubu arasında hiçbir parametrede istatistiksel fark yoktu (p>0,05). CO grubunda CAT, SOD ve NO ve Bcl-2 immünsüpresif hücre düzeyleri kontrol grubuna göre azaldı (tamamında p<0,001) ve ADMA ve MDA düzeyleri arttı (tamamında p<0,001). CO + DEX grubunda CO grubuna göre CAT, SOD ve NO düzeylerini istatistiksel olarak daha yüksekti (sırasıyla p:0,007; p:0,028; p:0,017).
Sonuç: CO zehirlenmesinden yarım saat sonra uygulanan DEX CAT, SOD ve NO gibi antioksidan yapıları arttırır. Buna bağlı olarak DEX’in CO zehirlenmesi için nöroprotektif bir etkisi olabilir.

Ethical Statement

Ankara Eğitim ve Araştırma Hastanesi Hayvan Deneyleri Yerel Etik Kurulu tarafından onaylanmıştır. (Onay No: 2022-0073).

References

  • Centers for Disease Control and Prevention (CDC). Unintentional non-fire-related carbon monoxide exposures—United States, 2001-2003. MMWR Morb Mortal Wkly Rep 2005;54:36-39.
  • Thom SR, Bhopale VM, Fisher D. Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicology and Applied Pharmacology 2006;213:152-159.
  • Prockop LD. Carbon monoxide brain toxicity: clinical, magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological effects in 9 people. Journal of Neuroimaging 2005;15:144-149.
  • Weaver LK. Clinical practice. Carbon monoxide poisoning. N Engl J Med 2009;360:1217-1225.
  • Geocadin RG, Koenig MA, Jia X, Stevens RD, Peberdy MA. Management of brain injury after resuscitation from cardiac arrest. Neurol Clin 2008;26:487-506.
  • Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage. Neuropharmacology 2008;55:310-318.
  • Liaquat Z, Xu X, Zilundu PLM, Fu R, Zhou L. The current role of dexmedetomidine as a neuroprotective agent: An updated review. Brain Sci 2021;11.
  • Barends CR, Absalom A, van Minnen B, Vissink A, Visser A. Dexmedetomidine versus midazolam in procedural sedation. A systematic review of efficacy and safety. PLoS One 2017;12:e0169525.
  • Weerink MAS, Struys M, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet 2017;56:893-913.
  • Hu Y, Zhou H, Zhang H, et al. The neuroprotective effect of dexmedetomidine and its mechanism. Front Pharmacol 2022;13:965661.
  • Wang X, Lei XG, Wang J. Malondialdehyde regulates glucose-stimulated insulin secretion in murine islets via TCF7L2-dependent Wnt signaling pathway. Mol Cell Endocrinol 2014;382:8-16.
  • Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014;2014:360438.
  • Sanyal J, Bandyopadhyay SK, Banerjee TK, et al. Plasma levels of lipid peroxides in patients with Parkinson’s disease. Eur Rev Med Pharmacol Sci 2009;13:129-132.
  • Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol 2001;54:176-186.
  • Góth L, Rass P, Páy A. Catalase enzyme mutations and their association with diseases. Mol Diagn 2004;8:141-149.
  • Raghavan SA, Dikshit M. Vascular regulation by the L-arginine metabolites, nitric oxide and agmatine. Pharmacol Res 2004;49:397-414.
  • Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000;20:2032-2037.
  • Richter B, Niessner A, Penka M, et al. Endurance training reduces circulating asymmetric dimethylarginine and myeloperoxidase levels in persons at risk of coronary events. Thromb Haemost 2005;94:1306-1311.
  • Jang JH, Surh YJ. Potentiation of cellular antioxidant capacity by Bcl-2: implications for its antiapoptotic function. Biochem Pharmacol 2003;66:1371-1379.
  • Susnow N, Zeng L, Margineantu D, Hockenbery DM. Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol 2009;19:42-49.
  • Kaufmann JA, Bickford PC, Taglialatela G. Oxidative-stress-dependent up-regulation of Bcl-2 expression in the central nervous system of aged Fisher-344 rats. J Neurochem 2001;76:1099-1108.
  • Zengin EN, Kayır S, Doğan G, et al. Neuroprotective effects of amantadine for experimental acute carbon monoxide poisoning. Eur Rev Med Pharmacol Sci 2022;26:6919-6927.
  • Fan DF, Hu HJ, Sun Q, et al. Neuroprotective effects of exogenous methane in a rat model of acute carbon monoxide poisoning. Brain Res 2016;1633:62-72.
  • Unchiti K, Leurcharusmee P, Samerchua A, Pipanmekaporn T, Chattipakorn N, Chattipakorn SC. The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies. Eur J Neurosci 2021;54(9):7006-7047.
  • Chen L, Cao J, Cao D, et al. Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury: An in vivo and in vitro study. Life Sci 2019;235:116553.

Neuroprotective Effects of Dexmedetomidine in Acute Carbon Monoxide Intoxication: An Experimental Study

Year 2025, Volume: 7 Issue: 1, 20 - 28, 25.02.2025
https://doi.org/10.52827/hititmedj.1485232

Abstract

Objective: It is aimed to evaluate the neuroprotective effects of Dexmedetomidine (DEX), which has antioxidant, antiapoptotic, anti-inflammatory properties, in acute carbon monoxide toxicity.
Material and Method: 28 Wistar-Albino female rats were randomly divided into four groups as control, Carbon monoxide (CO) poisoning, CO poisoning + DEX and DEX only. The rats in the study groups were exposed to 3000 ppm CO for 30 minutes. DEX was administered half an hour after the onset of CO exposure. At the end of the experiment, blood and tissue samples were taken from the sacrificed rats. Bcl-2 Immunopositively cell values in tissue samples taken from prefrontal and hippocampal areas were scored by examining immune expressions of Bcl-2 antibodies obtained by immunohistochemical method under light microscope. Malondialdehyde (MDA), nitric oxide (NO), asymmetric dimethylarginine ADMA levels, superoxide dismutase (SOD), and catalase (CAT) activity values were measured from blood and right hemisphere brain tissue samples by biochemical methods.
Results: CAT, SOD, MDA, ADMA and NO values were statistically different between the experimental groups (p<0.001). According to the post-hoc pairwise comparison test results, there was no statistical difference in any parameter between the DEX group alone and the control group (p>0.05). CAT, SOD and NO, and Bcl-2 immunosuppressive cell levels were decreased in the CO group compared to the control group (p<0.001 in all), while ADMA and MDA levels increased (p<0.001 in all). CAT, SOD, and NO levels were statistically higher in the CO + DEX group compared to the CO group (p:0.007; p:0.028; p:0.017, respectively).
Conclusion: DEX administered half an hour after CO poisoning increases antioxidant structures such as CAT, SOD and NO. Accordingly, DEX may have a neuroprotective effect for carbon monoxide poisoning.

Ethical Statement

Local Ethics Committee for Animal Experiments of Ankara Training and Research Hospital (Approval No: 2022-0073).

References

  • Centers for Disease Control and Prevention (CDC). Unintentional non-fire-related carbon monoxide exposures—United States, 2001-2003. MMWR Morb Mortal Wkly Rep 2005;54:36-39.
  • Thom SR, Bhopale VM, Fisher D. Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity. Toxicology and Applied Pharmacology 2006;213:152-159.
  • Prockop LD. Carbon monoxide brain toxicity: clinical, magnetic resonance imaging, magnetic resonance spectroscopy, and neuropsychological effects in 9 people. Journal of Neuroimaging 2005;15:144-149.
  • Weaver LK. Clinical practice. Carbon monoxide poisoning. N Engl J Med 2009;360:1217-1225.
  • Geocadin RG, Koenig MA, Jia X, Stevens RD, Peberdy MA. Management of brain injury after resuscitation from cardiac arrest. Neurol Clin 2008;26:487-506.
  • Doyle KP, Simon RP, Stenzel-Poore MP. Mechanisms of ischemic brain damage. Neuropharmacology 2008;55:310-318.
  • Liaquat Z, Xu X, Zilundu PLM, Fu R, Zhou L. The current role of dexmedetomidine as a neuroprotective agent: An updated review. Brain Sci 2021;11.
  • Barends CR, Absalom A, van Minnen B, Vissink A, Visser A. Dexmedetomidine versus midazolam in procedural sedation. A systematic review of efficacy and safety. PLoS One 2017;12:e0169525.
  • Weerink MAS, Struys M, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet 2017;56:893-913.
  • Hu Y, Zhou H, Zhang H, et al. The neuroprotective effect of dexmedetomidine and its mechanism. Front Pharmacol 2022;13:965661.
  • Wang X, Lei XG, Wang J. Malondialdehyde regulates glucose-stimulated insulin secretion in murine islets via TCF7L2-dependent Wnt signaling pathway. Mol Cell Endocrinol 2014;382:8-16.
  • Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014;2014:360438.
  • Sanyal J, Bandyopadhyay SK, Banerjee TK, et al. Plasma levels of lipid peroxides in patients with Parkinson’s disease. Eur Rev Med Pharmacol Sci 2009;13:129-132.
  • Young IS, Woodside JV. Antioxidants in health and disease. J Clin Pathol 2001;54:176-186.
  • Góth L, Rass P, Páy A. Catalase enzyme mutations and their association with diseases. Mol Diagn 2004;8:141-149.
  • Raghavan SA, Dikshit M. Vascular regulation by the L-arginine metabolites, nitric oxide and agmatine. Pharmacol Res 2004;49:397-414.
  • Cooke JP. Does ADMA cause endothelial dysfunction? Arterioscler Thromb Vasc Biol 2000;20:2032-2037.
  • Richter B, Niessner A, Penka M, et al. Endurance training reduces circulating asymmetric dimethylarginine and myeloperoxidase levels in persons at risk of coronary events. Thromb Haemost 2005;94:1306-1311.
  • Jang JH, Surh YJ. Potentiation of cellular antioxidant capacity by Bcl-2: implications for its antiapoptotic function. Biochem Pharmacol 2003;66:1371-1379.
  • Susnow N, Zeng L, Margineantu D, Hockenbery DM. Bcl-2 family proteins as regulators of oxidative stress. Semin Cancer Biol 2009;19:42-49.
  • Kaufmann JA, Bickford PC, Taglialatela G. Oxidative-stress-dependent up-regulation of Bcl-2 expression in the central nervous system of aged Fisher-344 rats. J Neurochem 2001;76:1099-1108.
  • Zengin EN, Kayır S, Doğan G, et al. Neuroprotective effects of amantadine for experimental acute carbon monoxide poisoning. Eur Rev Med Pharmacol Sci 2022;26:6919-6927.
  • Fan DF, Hu HJ, Sun Q, et al. Neuroprotective effects of exogenous methane in a rat model of acute carbon monoxide poisoning. Brain Res 2016;1633:62-72.
  • Unchiti K, Leurcharusmee P, Samerchua A, Pipanmekaporn T, Chattipakorn N, Chattipakorn SC. The potential role of dexmedetomidine on neuroprotection and its possible mechanisms: Evidence from in vitro and in vivo studies. Eur J Neurosci 2021;54(9):7006-7047.
  • Chen L, Cao J, Cao D, et al. Protective effect of dexmedetomidine against diabetic hyperglycemia-exacerbated cerebral ischemia/reperfusion injury: An in vivo and in vitro study. Life Sci 2019;235:116553.
There are 25 citations in total.

Details

Primary Language English
Subjects Anaesthesiology, Intensive Care
Journal Section Research Articles
Authors

Hüseyin Büyükkeskin 0009-0006-2899-3667

Güvenç Doğan 0000-0001-7351-8968

Selçuk Kayır 0000-0002-3176-7859

Ercan Ayaz 0000-0003-0429-0968

Yasin Kenesarı 0009-0008-8257-3414

Alperen Kısa 0000-0003-3699-2032

Sibel Önen Özdemir 0000-0001-6724-1675

Özgür Yağan 0000-0003-1596-1421

Publication Date February 25, 2025
Submission Date May 17, 2024
Acceptance Date October 13, 2024
Published in Issue Year 2025 Volume: 7 Issue: 1

Cite

AMA Büyükkeskin H, Doğan G, Kayır S, Ayaz E, Kenesarı Y, Kısa A, Önen Özdemir S, Yağan Ö. Neuroprotective Effects of Dexmedetomidine in Acute Carbon Monoxide Intoxication: An Experimental Study. Hitit Medical Journal. February 2025;7(1):20-28. doi:10.52827/hititmedj.1485232