Sıçan Epigastrik Ada Fleplerinde Edaravonun İskemi-Reperfüzyon Hasarına Karşı Koruyucu Etkisi: Deneysel Bir Çalışma
Öz
Amaç İskemi-reperfüzyon (I/R) hasarı, iskemik fazdan sonra kan dokuya geri döndüğünde meydana gelen doku hasarıdır. Reperfüzyon, hücre ölümü, doku bozukluğu ve nekroz ile sonuçlanan bir dizi akut inflamatuar süreç başlatır. Edaravone (3-meth-1-pheny1-2-pyrazolin-5-one) güçlü ve benzersiz bir sentetik radikal temizleyicidir. Bu araştırmada, edaravonun İ/R hasarı üzerindeki etkileri araştırıldı.
Gereç ve Yöntemler: 16 yetişkin erkek Sprague-Dawley sıçanı kullanıldı. Sekiz sıçan rastgele iki gruba ayrıldı. Grup 1 (kontrol grubu), tedavi olmaksızın 10 saat boyunca karın derisi flebine iskemi ve reperfüzyonu uygulandı. Grup 2'ye (tedavi grubu) iskemiden 10 saat önce intraperitoneal 3 mg/kg edaravon enjeksiyonu ve karın derisi flebinde reperfüzyon uygulandı. Planimetri kullanılarak flepler 1, 3, 7 ve 10 günlük aralıklarla incelendi. Daha sonra biyokimyasal (doku glutatyonu [GSH], doku proteini, lipid peroksidasyonu [MDA] ve nitrik oksit [NO] düzeylerinin ölçümü) ve histopatolojik (doku glutatyonu [GSH], doku proteini, lipid peroksidasyonu ölçümü) için flepler çıkarıldı. MDA] ve nitrik oksit [NO] seviyeleri)
Bulgular: Grup 1 ve 2 arasında NO, MDA, GSH veya planimetrik analizler açısından anlamlı bir değişiklik (p > 0.05) bulamadık. Grup 2, grup 1'den daha düşük nötrofil sayısına sahipti, ancak fark istatistiksel olarak anlamlı değildi (p > 0.05).
Sonuç Edaravone çok etkili bir antioksidandır. Yine de araştırmamız, bir deri flep modelinde I/R hasarını etkilemeyebileceğini gösteriyor.
Anahtar Kelimeler
Kaynakça
- References
- 1. Hinder RA, Stein HJ. Oxygen derived free radicals. Arch Surg. 1991; 126:104e5.
- 2. Kasprzak KS. Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis. Free Radic Biol Med. 2002;32(10):958e67.
- 3. Kim EK, Hong JP. The effect of recombinant human erythropoietin on ischemia-reperfusion injury: an experimental study in a rat TRAM flap model. Plast Reconstr Surg. 2007 Dec;120(7):1774e81.
- 4. Yao LH, Jiang YM, Shi J, Toma´s-Barbera´n FA, Datta N, Singanusong R, Chen SS, et al. Flavonoids in food and their health benefits. Plant Foods Hum Nutr. 2004; 59:113e22.
- 5. Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N, Tada N. Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev. 2006;12(1):9-20.
- 6. Shichinohe H, Kuroda S, Yasuda H, Ishikawa T, Iwai M, Horiuchi M, Iwasaki Y. Neuroprotective effects of the free radical scavenger Edaravone (MCI-186) in mice permanent focal brain ischemia. Brain Res. 2004;1029(2):200-06.
- 7. Zhang N, Komine-Kobayashi M, Tanaka R, Liu M, Mizuno Y, Urabe T. Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke 2005;36(10):2220-25.
- 8. Group EABIS. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis. 2003;15(3):222-29.
- 9. C, Marie C, Beley A. Importance of iron location in iron-induced hydroxyl radical Demougeot production by brain slices. Life Sci. 2000; 67:399-410.
- 10. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82:70-77.
- 11. Ersel M, Uyanikgil Y, Akarca FK, Ozcete E, Altunci YA, Karabey F, Cavusoglu T, Meral A, Yigitturk G, Cetin EO. Effects of silk sericin on incision wound healing in a dorsal skin flap wound healing rat model. Med Sci Monit. 2016; 22:1064-78.
- 12. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190(3):255-66.
- 13. Akdemir, O., Tatar, B.E., Gökhan, A. et al. Preventive effect of trimetazidine against ischemia-reperfusion injury in rat epigastric island flaps: an experimental study. Eur J Plast Surg. 2021;44:177-88.
- 14. Zhao G, Zhang X, Xu P, Mi J-Y, Rui Y-J. The protective effect of irisin against ischemia-reperfusion injury after perforator flap grafting in rats. Injury 2018;49(12):2147-53.
- 15. Liu H, Zhang M, Dong X, Liu Y, Hao Y, Wang Y. Necrostatin-1 protects against ischemia/reperfusion injury by inhibiting receptor-interacting protein 1 in a rat flap model. J Plast Reconstr Aesthet Surg. 2019;72(2):194-202.
- 16. Petrovics L, Nagy T, Hardi P, Bognar L, Pavlovics G, Tizedes G, Takacs I, Jancso G. The effect of trimetazidine in reducing the ischemia-reperfusion injury in rat epigastric skin flaps. Clin Hemorheol Microcirc. 2018;69(3):405-15.
- 17. Ballestín A, Casado JG, Abellán E, Vela FJ, Álvarez V, Usón A, López E, Marinaro F, Blázquez R, Sánchez-Margallo FM. Ischemia-reperfusion injury in a rat microvascular skin free flap model: a histological, genetic, and blood flow study. PLoS One. 2018;13(12):e0209624.
- 18. Akdemir O, Hede Y, Zhang F, Lineaweaver WC, Arslan Z, Songur E. Effects of taurine on reperfusion injury. J Plast Reconstr Aesthet Surg. 2011 Jul;64(7):921-28.
- 19. Yoshida WB, Bueno Pires de Campos E. Ischemia and reperfusion in skin flaps: effects of mannitol and vitamin C in reducing necrosis area in a rat experimental model. Acta Cir Bras. 2005;20(5):358-63.
- 20. Zaccaria A, Weinzweig N, Yoshitake M, Matsuda T, Cohen M. Vitamin C reduces ischemia-reperfusion injury in a rat epigastric island skin flap model. Ann Plast Surg. 1994;33(6):620-23.
- 21. Çetin C, Köse AA, Aral E, Çolak Ö, Erçel C, Karabagli Y, Özyilmaz M, Alatas Ö, Eker A. Protective effect of fucoidan (a neutrophil rolling inhibitor) on ischemia reperfusion injury: experimental study in rat epigastric island flaps. Ann Plast Surg. 2001;47(5):540-46.
- 22. Cordeiro PG, Mastorakos DP, Hu Q-Y, Kirschner RE. The protective effect of L-arginine on ischemia-reperfusion injury in rat skin flaps. Plast Reconstr Surg. 1997;100(5):1227-33.
- 23. van den Heuvel MG, Buurman WA, Bast A, van der Hulst RR. Review: ischaemia–reperfusion injury in flap surgery. J Plast Reconstr Aesthet Surg. 2009;62(6):721-26.
- 24. Omori K, Shikata Y, Sarai K, Watanabe N, Wada J, Goda N, Kataoka N, Shikata K, Makino H. Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells. Am J Physiol Cell Physiol. 2007;293(5):C1523-31.
- 25. Zhang D, Kang S, Zhang Z, et al. Edaravone enhances the viability of ischemia/reperfusion flaps. J Huazhong Univ Sci Technol. [Med Sci] 2017; 37:51-56.
- 26. Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Brit Med Bull. 2004; 70:71-86.
- 27. Coban YK, Ergun Y, Ciralik H. Depletion of glutathione by buthionine sulfoximine decreases random-pattern skin flap viability in rats. J Surg Res. 2007;143(2):247-52.
- 28. Schulz R, Kelm M, Heusch G. Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovasc Res. 2004;61(3):402-13.
- 29. Schofield ZV, Woodruff TM, Halai R, Wu MC-L, Cooper MA. Neutrophils—a key component of ischemia-reperfusion injury. Shock 2013;40(6):463-70.
- 30. Grommes J, Soehnlein O. Contribution of neutrophils to acute lung injury. Mol Med. 2011;17(3):293-307.
- 31. El-Benna J, Dang PM-C, Gougerot-Pocidalo M-A. Priming of the neutrophilNADPH oxidase activation: role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane. Semin Immunopathol. 2008; 30:279-89.
- 32. Fialkow L, Wang Y, Downey GP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med. 2007;42(2):153-64.
Preventive Effect of Edaravone Against Ischemia-Reperfusion Injury in Rat Epigastric Island Flaps: An Experimental Study
Öz
Objective Ischemia-reperfusion (I/R) injury is tissue damage occurring when blood returns to a tissue after an ischemic phase. Reperfusion initiates a cascade of acute inflammatory processes that end in cell death, tissue malfunction, and necrosis. Edaravone (3-methy-1-pheny1-2-pyrazolin-5-one) is a powerful and unique synthetic radical scavenger. In this research, the effects of edaravone on I/R damage were investigated.
Material and Methods: 16 adult male Sprague–Dawley rats were utilized. Eight rats were allocated at random into two groups. Group 1 (the control group) experienced ischemia and reperfusion of an abdominal skin flap for 10 hours without therapy. Group 2 (treatment group) received an intraperitoneal injection of 3 mg/kg edaravone 10 hours prior to ischemia and reperfusion in an abdominal skin flap. Using planimetry, flaps were examined at intervals of 1, 3, 7, and 10 days. Then, flaps were removed for biochemical (measurement of tissue glutathione [GSH], tissue protein, lipid peroxidation [MDA], and nitric oxide [NO] levels) and histopathological (measurement of tissue glutathione [GSH], tissue protein, lipid peroxidation [MDA], and nitric oxide [NO] levels)
Results: We found no significant changes (p > 0.05) between groups 1 and 2 in terms of NO, MDA, GSH, or planimetric analyses. Group 2 had a lower neutrophil count than group 1, however the difference was not statistically significant (p > 0.05).
Conclusion Edaravone is a very effective antioxidant. Nevertheless, our research indicates that it may not influence I/R damage in a skin flap model.
Anahtar Kelimeler
Kaynakça
- References
- 1. Hinder RA, Stein HJ. Oxygen derived free radicals. Arch Surg. 1991; 126:104e5.
- 2. Kasprzak KS. Oxidative DNA and protein damage in metal-induced toxicity and carcinogenesis. Free Radic Biol Med. 2002;32(10):958e67.
- 3. Kim EK, Hong JP. The effect of recombinant human erythropoietin on ischemia-reperfusion injury: an experimental study in a rat TRAM flap model. Plast Reconstr Surg. 2007 Dec;120(7):1774e81.
- 4. Yao LH, Jiang YM, Shi J, Toma´s-Barbera´n FA, Datta N, Singanusong R, Chen SS, et al. Flavonoids in food and their health benefits. Plant Foods Hum Nutr. 2004; 59:113e22.
- 5. Yoshida H, Yanai H, Namiki Y, Fukatsu-Sasaki K, Furutani N, Tada N. Neuroprotective effects of edaravone: a novel free radical scavenger in cerebrovascular injury. CNS Drug Rev. 2006;12(1):9-20.
- 6. Shichinohe H, Kuroda S, Yasuda H, Ishikawa T, Iwai M, Horiuchi M, Iwasaki Y. Neuroprotective effects of the free radical scavenger Edaravone (MCI-186) in mice permanent focal brain ischemia. Brain Res. 2004;1029(2):200-06.
- 7. Zhang N, Komine-Kobayashi M, Tanaka R, Liu M, Mizuno Y, Urabe T. Edaravone reduces early accumulation of oxidative products and sequential inflammatory responses after transient focal ischemia in mice brain. Stroke 2005;36(10):2220-25.
- 8. Group EABIS. Effect of a novel free radical scavenger, edaravone (MCI-186), on acute brain infarction. Randomized, placebo-controlled, double-blind study at multicenters. Cerebrovasc Dis. 2003;15(3):222-29.
- 9. C, Marie C, Beley A. Importance of iron location in iron-induced hydroxyl radical Demougeot production by brain slices. Life Sci. 2000; 67:399-410.
- 10. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959; 82:70-77.
- 11. Ersel M, Uyanikgil Y, Akarca FK, Ozcete E, Altunci YA, Karabey F, Cavusoglu T, Meral A, Yigitturk G, Cetin EO. Effects of silk sericin on incision wound healing in a dorsal skin flap wound healing rat model. Med Sci Monit. 2016; 22:1064-78.
- 12. Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190(3):255-66.
- 13. Akdemir, O., Tatar, B.E., Gökhan, A. et al. Preventive effect of trimetazidine against ischemia-reperfusion injury in rat epigastric island flaps: an experimental study. Eur J Plast Surg. 2021;44:177-88.
- 14. Zhao G, Zhang X, Xu P, Mi J-Y, Rui Y-J. The protective effect of irisin against ischemia-reperfusion injury after perforator flap grafting in rats. Injury 2018;49(12):2147-53.
- 15. Liu H, Zhang M, Dong X, Liu Y, Hao Y, Wang Y. Necrostatin-1 protects against ischemia/reperfusion injury by inhibiting receptor-interacting protein 1 in a rat flap model. J Plast Reconstr Aesthet Surg. 2019;72(2):194-202.
- 16. Petrovics L, Nagy T, Hardi P, Bognar L, Pavlovics G, Tizedes G, Takacs I, Jancso G. The effect of trimetazidine in reducing the ischemia-reperfusion injury in rat epigastric skin flaps. Clin Hemorheol Microcirc. 2018;69(3):405-15.
- 17. Ballestín A, Casado JG, Abellán E, Vela FJ, Álvarez V, Usón A, López E, Marinaro F, Blázquez R, Sánchez-Margallo FM. Ischemia-reperfusion injury in a rat microvascular skin free flap model: a histological, genetic, and blood flow study. PLoS One. 2018;13(12):e0209624.
- 18. Akdemir O, Hede Y, Zhang F, Lineaweaver WC, Arslan Z, Songur E. Effects of taurine on reperfusion injury. J Plast Reconstr Aesthet Surg. 2011 Jul;64(7):921-28.
- 19. Yoshida WB, Bueno Pires de Campos E. Ischemia and reperfusion in skin flaps: effects of mannitol and vitamin C in reducing necrosis area in a rat experimental model. Acta Cir Bras. 2005;20(5):358-63.
- 20. Zaccaria A, Weinzweig N, Yoshitake M, Matsuda T, Cohen M. Vitamin C reduces ischemia-reperfusion injury in a rat epigastric island skin flap model. Ann Plast Surg. 1994;33(6):620-23.
- 21. Çetin C, Köse AA, Aral E, Çolak Ö, Erçel C, Karabagli Y, Özyilmaz M, Alatas Ö, Eker A. Protective effect of fucoidan (a neutrophil rolling inhibitor) on ischemia reperfusion injury: experimental study in rat epigastric island flaps. Ann Plast Surg. 2001;47(5):540-46.
- 22. Cordeiro PG, Mastorakos DP, Hu Q-Y, Kirschner RE. The protective effect of L-arginine on ischemia-reperfusion injury in rat skin flaps. Plast Reconstr Surg. 1997;100(5):1227-33.
- 23. van den Heuvel MG, Buurman WA, Bast A, van der Hulst RR. Review: ischaemia–reperfusion injury in flap surgery. J Plast Reconstr Aesthet Surg. 2009;62(6):721-26.
- 24. Omori K, Shikata Y, Sarai K, Watanabe N, Wada J, Goda N, Kataoka N, Shikata K, Makino H. Edaravone mimics sphingosine-1-phosphate-induced endothelial barrier enhancement in human microvascular endothelial cells. Am J Physiol Cell Physiol. 2007;293(5):C1523-31.
- 25. Zhang D, Kang S, Zhang Z, et al. Edaravone enhances the viability of ischemia/reperfusion flaps. J Huazhong Univ Sci Technol. [Med Sci] 2017; 37:51-56.
- 26. Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Brit Med Bull. 2004; 70:71-86.
- 27. Coban YK, Ergun Y, Ciralik H. Depletion of glutathione by buthionine sulfoximine decreases random-pattern skin flap viability in rats. J Surg Res. 2007;143(2):247-52.
- 28. Schulz R, Kelm M, Heusch G. Nitric oxide in myocardial ischemia/reperfusion injury. Cardiovasc Res. 2004;61(3):402-13.
- 29. Schofield ZV, Woodruff TM, Halai R, Wu MC-L, Cooper MA. Neutrophils—a key component of ischemia-reperfusion injury. Shock 2013;40(6):463-70.
- 30. Grommes J, Soehnlein O. Contribution of neutrophils to acute lung injury. Mol Med. 2011;17(3):293-307.
- 31. El-Benna J, Dang PM-C, Gougerot-Pocidalo M-A. Priming of the neutrophilNADPH oxidase activation: role of p47phox phosphorylation and NOX2 mobilization to the plasma membrane. Semin Immunopathol. 2008; 30:279-89.
- 32. Fialkow L, Wang Y, Downey GP. Reactive oxygen and nitrogen species as signaling molecules regulating neutrophil function. Free Radic Biol Med. 2007;42(2):153-64.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Original Article |
| Yazarlar | |
| Erken Görünüm Tarihi | 30 Nisan 2023 |
| Yayımlanma Tarihi | 30 Nisan 2023 |
| Gönderilme Tarihi | 29 Eylül 2022 |
| Yayımlandığı Sayı | Yıl 2023 Cilt: 33 Sayı: 2 |
Genel Tıp Dergisi Creative Commons Atıf-GayriTicari 4.0 Uluslararası Lisansı (CC BY NC) ile lisanslanmıştır.