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The Effect of Dexmedetomidine on Oxidative Balance in Lung, Liver and Heart: Rat Sepsis Model

Yıl 2023, , 95 - 99, 28.02.2023
https://doi.org/10.54005/geneltip.1224337

Öz

Aim: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Early intervention in sepsis is vital and research on the subject continues. Having sedative, analgesic, and anxiolytic properties, Dexmedetomidine (DEX) is a potent lipophilic α2‐adrenoceptor agonist with imidazole structure. In recent years, there has been an increasing number of studies on the organ protective effects of DEX. Unlike other studies, in this project proposal, it was aimed to investigate the effect of DEX applied in different periods of sepsis on the oxidative stress index in the lungs, liver and heart.
Material and methods: The study was approved by the Necmettin Erbakan University Experimental Animals Ethics Committee (2020 – 017). In the study, 50 female wistar albino rats were used as experimental animals. Animals were divided into five groups: 1st group: SHAM (n:10), 2nd group: SEPSIS (n:10), 3rd group: DEX (PreDEX, n:10) applied 30 minutes before cecal ligation puncture (CLP) procedure, group 4: DEX administered 12 hours after CLP (Post12DEX, n:10), group 5: DEX administered 24 hours after CLP (Post24DEX, n:10).
Results: In liver and heart tissues, the decrease in total antioxidant status (TAS) levels in the SEPSIS group was statistically significant compared to the Post12DEX (p <0.001 and p <0.001) and Post24DEX (p =0.007 and p <0.05) groups. In lung, liver and heart tissues, the increase in the oxidative stress index (OSI) levels in the SEPSIS group, compared to the PreDEX (p =0.007, p =0.003, p <0.001) group, was statistically significant.
Conclusion: DEX applied until the 24th hour after CLP for liver tissue contributes positively to reducing the OSI index of DEX applied until the 12th hour for heart tissue, but it contributes to reducing the DEX OSI index applied only before CLP for lung tissue.

Kaynakça

  • Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov 1;47(11):1181-1247.
  • Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). Vol. 315, JAMA - Journal of the American Medical Association. American Medical Association; 2016. p. 801–810.
  • Xu J, Lei S, Ye G. Dexmedetomidine attenuates oxidative/nitrative stress in lung tissues of septic mice partly via activating heme oxygenase‑1. Exp Ther Med. 2019 Oct;18(4):3071-3077.
  • Ramírez M. Multiple organ dysfunction syndrome. Curr Probl Pediatr Adolesc Health Care. 2013 Nov;43(10):273-277.
  • Zeng X, Wang H, Xing X, Wang Q, Li W. Dexmedetomidine protects against transient global cerebral ischemia/reperfusion induced oxidative stress and inflammation in diabetic rats. PLoS One. 2016 Mar 1;11(3):e0151620.
  • Cho JS, Shim JK, Soh S, Kim MK, Kwak YL. Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery. Kidney Int. 2016 Mar 1;89(3):693–700.
  • Chen Y, Feng X, Hu X, Sha J, Li B, Zhang H, et al. Dexmedetomidine ameliorates acute stress-induced kidney injury by attenuating oxidative stress and apoptosis through inhibition of the ROS/JNK signaling pathway. Oxid Med Cell Longev. 2018 Sep 3;2018:4035310.
  • Li X-K, Yang S-C, Bi L, Jia Z. Effects of dexmedetomidine on sepsis-induced liver injury in rats. Eur Rev Med Pharmacol Sci. 2019;23(3):177-183.
  • Zhang J, Wang Z, Wang Y, Zhou G, Li H. The effect of dexmedetomidine on inflammatory response of septic rats. BMC Anesthesiol. 2015 May 1;15:68.
  • Koca U, Olguner ÇG, Ergür BU, Altekin E, Taşdöğen A, Duru S, et al. The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis. Sci World J. 2013;2013:1-11.
  • Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, et al. Dexmedetomidine Inhibits Inflammatory Reaction in Lung Tissues of Septic Rats by Suppressing TLR4/NF-κB Pathway. Mediators Inflamm. 2013;2013:1-9.
  • Zhang J, Peng K, Zhang J, Meng X, Ji F. Dexmedetomidine preconditioning may attenuate myocardial ischemia/reperfusion injury by down-regulating the HMGB1-TLR4-MyD88-NF-кB signaling pathway. PLoS One. 2017 Feb 21;12(2):e0172006.
  • Hofer S, Steppan J, Wagner T, Funke B, Lichtenstern C, Martin E, et al. Central sympatholytics prolong survival in experimental sepsis. Crit Care. 2009;13(1):R11.
  • Peng Z-Y, Zhou F, Kellum JA. Cross-species validation of cell cycle arrest markers for acute kidney injury in the rat during sepsis. Intensive Care Med Exp. 2016 Dec;4(1):12.
  • Kocabas R, Akoz M. The effects of vitamin D supplementation on healthy and hypercholesterolemic rabbits on levels of OSI and paraoxonase. Turk J Biochem. 2018;43(5):549-556.
  • Flanders CA, Rocke AS, Edwardson SA, Baillie JK, Walsh TS. The effect of dexmedetomidine and clonidine on the inflammatory response in critical illness: a systematic review of animal and human studies. Crit Care. 2019 Dec 11;23(1):402.
  • Chen J-H, Yu G-F, Jin S-Y, Zhang W-H, Lei D-X, Zhou S-L, et al. Activation of α2 adrenoceptor attenuates lipopolysaccharide-induced hepatic injury. Int J Clin Exp Pathol. 2015;8(9):10752–10759.
  • Kong W, Kang K, Gao Y, Liu H, Meng X, Yang S, et al. Dexmedetomidine alleviates LPS-induced septic cardiomyopathy via the cholinergic anti-inflammatory pathway in mice. Am J Transl Res. 2017;9(11):5040-5047.
  • Zhang T, Mei Q, Dai S, Liu Y, Zhu H. Use of dexmedetomidine in patients with sepsis: a systematic review and meta-analysis of randomized-controlled trials. Annals of Intensive Care. 2022 Aug 27;12(1):81.

Deksmedetomidinin Akciğer, Karaciğer ve Kalpteki Oksidatif Dengeye Etkisi: Sıçan Sepsis Modeli

Yıl 2023, , 95 - 99, 28.02.2023
https://doi.org/10.54005/geneltip.1224337

Öz

Amaç: Sepsis, enfeksiyona karşı düzensiz konak yanıtının neden olduğu yaşamı tehdit eden, organ disfonksiyonudur. Sepsise erken müdahale hayati önem arz etmekte ve konuyla ilgili araştırmalar devam etmektedir. Deksmedetomidin (DEX), sedatif, analjezik, anksiyolitik özelliklere sahip imidazol yapıya sahip olan güçlü bir lipofilik α2 ‐ adrenoseptör agonistidir. Son yıllarda DEX’in organ koruyucu etkileri ile ilgili artan sayıda çalışma mevcuttur. Bu proje önerisinde; diğer çalışmalardan farklı olarak sepsisin farklı dönemlerinde uygulanan DEX’in; akciğer, karaciğer ve kalpte oluşan oksidatif stres indeksine etkisini araştırmak amaçlanmıştır.
Materyal ve metod: Çalışma için Necmettin Erbakan Üniversitesi Deney Hayvanları Etik Kurulundan (2020 – 017) onay alındı. Çalışmada deney hayvanı olarak 50 adet dişi wistar albino sıçan kullanıldı. Hayvanlar beş gruba ayrıldı: 1. grup: SHAM (n:10), 2. grup: SEPSİS (n:10), 3. grup: Çekal ligasyon puncture (CLP) işleminden 30 dakika önce DEX (PreDEX, n:10) uygulanan, 4. grup: CLP’den 12. saat sonra DEX uygulanan (Post12DEX, n:10), 5. grup: CLP’den 24. saat sonra DEX uygulanan grup (Post24DEX, n:10) olarak tasarlandı.
Bulgular: Karaciğer ve Kalp dokularında; Post12DEX (p <0.001 ve p <0.001) ve Post24DEX (p =0.007 ve p <0.05) gruplarına göre SEPSİS grubunda TAS seviyelerindeki azalma istatiksel değerlendirme açıdan anlamlı bulundu. Akciğer, Karaciğer ve Kalp dokularında; PreDEX (p =0.007, p =0.003, p <0.001) grubuna göre SEPSİS grubundaki OSI seviyelerindeki artma istatiksel değerlendirme açıdan anlamlıydı.
Sonuç: Karaciğer dokusu için CLP sonrası 24. saatte kadar uygulanan DEX, Kalp dokusu için 12. saate kadar uygulanan DEX’in bu dokulardaki OSI indeksini azaltmaya olumlu katkı sağlamakta fakat akciğer dokusu için sadece CLP öncesi uygulanan DEX OSI indeksini azaltmaya katkı sağlamaktadır.

Kaynakça

  • Evans L, Rhodes A, Alhazzani W, Antonelli M, Coopersmith CM, French C, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021. Intensive Care Med. 2021 Nov 1;47(11):1181-1247.
  • Singer M, Deutschman CS, Seymour C, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). Vol. 315, JAMA - Journal of the American Medical Association. American Medical Association; 2016. p. 801–810.
  • Xu J, Lei S, Ye G. Dexmedetomidine attenuates oxidative/nitrative stress in lung tissues of septic mice partly via activating heme oxygenase‑1. Exp Ther Med. 2019 Oct;18(4):3071-3077.
  • Ramírez M. Multiple organ dysfunction syndrome. Curr Probl Pediatr Adolesc Health Care. 2013 Nov;43(10):273-277.
  • Zeng X, Wang H, Xing X, Wang Q, Li W. Dexmedetomidine protects against transient global cerebral ischemia/reperfusion induced oxidative stress and inflammation in diabetic rats. PLoS One. 2016 Mar 1;11(3):e0151620.
  • Cho JS, Shim JK, Soh S, Kim MK, Kwak YL. Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery. Kidney Int. 2016 Mar 1;89(3):693–700.
  • Chen Y, Feng X, Hu X, Sha J, Li B, Zhang H, et al. Dexmedetomidine ameliorates acute stress-induced kidney injury by attenuating oxidative stress and apoptosis through inhibition of the ROS/JNK signaling pathway. Oxid Med Cell Longev. 2018 Sep 3;2018:4035310.
  • Li X-K, Yang S-C, Bi L, Jia Z. Effects of dexmedetomidine on sepsis-induced liver injury in rats. Eur Rev Med Pharmacol Sci. 2019;23(3):177-183.
  • Zhang J, Wang Z, Wang Y, Zhou G, Li H. The effect of dexmedetomidine on inflammatory response of septic rats. BMC Anesthesiol. 2015 May 1;15:68.
  • Koca U, Olguner ÇG, Ergür BU, Altekin E, Taşdöğen A, Duru S, et al. The Effects of Dexmedetomidine on Secondary Acute Lung and Kidney Injuries in the Rat Model of Intra-Abdominal Sepsis. Sci World J. 2013;2013:1-11.
  • Wu Y, Liu Y, Huang H, Zhu Y, Zhang Y, Lu F, et al. Dexmedetomidine Inhibits Inflammatory Reaction in Lung Tissues of Septic Rats by Suppressing TLR4/NF-κB Pathway. Mediators Inflamm. 2013;2013:1-9.
  • Zhang J, Peng K, Zhang J, Meng X, Ji F. Dexmedetomidine preconditioning may attenuate myocardial ischemia/reperfusion injury by down-regulating the HMGB1-TLR4-MyD88-NF-кB signaling pathway. PLoS One. 2017 Feb 21;12(2):e0172006.
  • Hofer S, Steppan J, Wagner T, Funke B, Lichtenstern C, Martin E, et al. Central sympatholytics prolong survival in experimental sepsis. Crit Care. 2009;13(1):R11.
  • Peng Z-Y, Zhou F, Kellum JA. Cross-species validation of cell cycle arrest markers for acute kidney injury in the rat during sepsis. Intensive Care Med Exp. 2016 Dec;4(1):12.
  • Kocabas R, Akoz M. The effects of vitamin D supplementation on healthy and hypercholesterolemic rabbits on levels of OSI and paraoxonase. Turk J Biochem. 2018;43(5):549-556.
  • Flanders CA, Rocke AS, Edwardson SA, Baillie JK, Walsh TS. The effect of dexmedetomidine and clonidine on the inflammatory response in critical illness: a systematic review of animal and human studies. Crit Care. 2019 Dec 11;23(1):402.
  • Chen J-H, Yu G-F, Jin S-Y, Zhang W-H, Lei D-X, Zhou S-L, et al. Activation of α2 adrenoceptor attenuates lipopolysaccharide-induced hepatic injury. Int J Clin Exp Pathol. 2015;8(9):10752–10759.
  • Kong W, Kang K, Gao Y, Liu H, Meng X, Yang S, et al. Dexmedetomidine alleviates LPS-induced septic cardiomyopathy via the cholinergic anti-inflammatory pathway in mice. Am J Transl Res. 2017;9(11):5040-5047.
  • Zhang T, Mei Q, Dai S, Liu Y, Zhu H. Use of dexmedetomidine in patients with sepsis: a systematic review and meta-analysis of randomized-controlled trials. Annals of Intensive Care. 2022 Aug 27;12(1):81.
Toplam 19 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Klinik Tıp Bilimleri
Bölüm Original Article
Yazarlar

Rahim Kocabaş 0000-0001-8006-284X

Sinan Oğuzhan Ulukaya 0000-0002-4217-6114

Eyüp Fatih Cihan 0000-0003-3307-1174

Alper Yosunkaya 0000-0003-2525-4480

Yayımlanma Tarihi 28 Şubat 2023
Gönderilme Tarihi 26 Aralık 2022
Yayımlandığı Sayı Yıl 2023

Kaynak Göster

Vancouver Kocabaş R, Ulukaya SO, Cihan EF, Yosunkaya A. The Effect of Dexmedetomidine on Oxidative Balance in Lung, Liver and Heart: Rat Sepsis Model. Genel Tıp Derg. 2023;33(1):95-9.

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