Araştırma Makalesi
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Karaciğer İskemisinde Karnozinin Koruyucu Etkisi

Yıl 2020, Cilt: 42 Sayı: 3, 269 - 276, 27.05.2020
https://doi.org/10.20515/otd.481714

Öz

Bu çalışmada, biyokimyasal ve
histopatolojik değerlendirme kullanılarak karaciğer iskemisi-reperfüzyon (İ /
R) hasarına maruz kalan sıçanlarda karnosinin (CAR) antioksidan etkileri
araştırıldı. Karnosinin karaciğer üzerindeki antioksidan etkilerini araştırmak
için 200-250 gr ağırlığındaki yirmi dört Sprague-Dawley erkek sıçan kullanıldı.
Sıçanlar rastgele aşağıdaki gruplara ayrıldı: Kontrol grubu (G1), hepatik I / R
grubu (G2) ve 100 mg / kg CAR ile tedavi edilen hepatik I / R grubu (G3). Kontrol
grubundaki sıçanlara sadece laparotomi ve kateterizasyon uygulandı. Diğer
gruplardaki ler, laparotomi sonrası hepatik arter klemplenmesi ile 1 saat
hepatik iskemi sonrasında 2 saat reperfüzyona maruz bırakıldı. Tedavi
grubundaki farelere, hepatik arter klemplenmeden 60 dakika önce 100 mg / kg CAR
60 dakika intraperitoneal enjeksiyon olarak  
yapıldı. Tüm sıçanlar 48 saat izlendi. Daha
sonra sacrifiye edilip aspartat transaminaz (AST), alanin transaminaz (ALT)
tayini için kan örnekleri alındı ​​ve malondialdehit (MDA), glutatyon (GSH) ve
katalaz (CAT) seviyelerin ölçmek için ve histopatolojik incelemeiçin
 karaciğer doku örnekleri alındı.  Tedavi grubunda Serum AST, ALT ve doku MDA
düzeyleri anlamlı olarak azaldı ve GSH ve CAT düzeyleri CAR ile tedavi edilen
grupta, sadece I / R yaralanmasına maruz kalan tedavi edilmeyen grupla
karşılaştırıldığında anlamlı olarak daha yüksekti. Karnosin alan sıçanlarda
histopatolojik hasar, tedavi edilmeyen gruba göre anlamlı derecede azdı.
 Bu çalışma sonucunda 100 mg / kg CAR'ın, İ / R
hasarı nedeniyle karaciğer dokusunda oksidatif hasarı önlemede etkili
olabileceği sonucuna vardık.

Kaynakça

  • 1. Carden and Granger. Pathophysiology of ischemia-reperfusion injury. Pathol, 2000; 190: 255–266.
  • 2. Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol, 2003; 18: 891–902.
  • 3. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry and Cell Biology. 2007; 39(1): 44–84. doi: 10.1016/j.biocel.2006.07.001.
  • 4. Golubović S, Stanković I, Ristić L, Cosić V, Dordević I, Radović M. Antioxidant enzymes and lipid peroxidation products in patients with pulmonary tuberculosis. Med Pregl. 2010; 63: 450-3.
  • 5. Abdel-Gaber SA, Ibrahim MA, Amin EF, Ibrahim SA, Mohammed RK, Abdelrahman AM. Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats. Life Sci. 2015; 134(1): 42-8. doi: 10.1016/j.lfs.2015.04.025.
  • 6. Fouad AA, El-RehanyMA, Maghraby HK. The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rats. Eur J Pharmacol. 2007 Oct 15;572(1):61-8. Epub 2007 Jun 15
  • 7. Yamashita S, Sato M, Matsumoto T et al Mechanisms of carnosine-induced activation of neuronal cells. Biosci Biotechnol Biochem. 2017 Dec 11:1-6
  • 8. Sahin S,Burukoglu Donmez D. Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of Acute Kidney Injury Due to Septic Shock. Med Sci Monit. 2018 Jan 15;24:305-316.
  • 9. Jamshidzadeh A, Heidari R, Latifpour Z et al Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats. Clin Res Hepatol Gastroenterol. 2017 Sep;41(4):424-434
  • 10. Qi B, Wang J, Ma YB, Wu SG.Effect of dietary β-alanine supplementation on growth performance, meat quality, carnosinecontent, and gene expression of carnosine-related enzymes in broilers.Poult Sci. 2018 Jan 6. doi: 10.3382/ps/pex410
  • 11. Nakagawa K, Kawagoe M, Yoshimura M, Arata H, Minamikawa T, Nakamura M. Differential effects of flavonoid carnosine on oxidative damages induced by hydrophilic and lipophilic radical generator in hepatic Iysosomal fractions of mice. J. Health Science, 2000; 46: 509-512.
  • 12. Yabe Y, Kobayashi N, Nishihashi T, Takahashi R, Nishikawa M, Takakura Y. et al. Prevention of neutrofil-mediated hepatic ischemia-reperfusion injury by Superoxide dismutase and Catalase derivatives. J. Pharmacol. Exp. Ther. 2001; 298: 894-899.
  • 13. Singh D, Chander V, Chopra K. The effect of carnosine, a bioflavonoid on ischemia/reperfusion induced renal injury in rats. Arch Med Res. 2008; 39(7): 714.
  • 14. Peralta C, Bartrons R, Serafin A, Blazquez C, Guzman M, Prats N. et al. Adenosine Monophosphate–Activated Protein Kinase Mediates the Protective Effects of Ischemic Preconditioning on Hepatic Ischemia-Reperfusion Injury in the Rat. Hepatology. 2001; 34(6): 1164-1173.
  • 15. Cuzzocrea, G. Costantino, E. Mazzon, A. Micali, A. De Sarro, A.P.CaputiBenefical effects of melatonin in a rat model of splanchnic artery occlusion and reperfusion J Pineal Res, 28 (2000), pp. 52-63
  • 16. Fan FY, Huang LZ, Wang GY, Zheng W, Wang B, Zhou H, Wang ZL. Effect of carnosine on prevention of reperfusion liver injury during hemorrhagic shock and reperfusion in rats. Article in Chinese. Zhonghua Gan Zang Bing Za Zhi. 2006; 14(12): 942-3.
  • 17. Artun BC, Küskü Kiraz Z, Güllüoğlu M, Cevikbaş U, Koçak Toker N, Uysal M. The effect of carnosine pretreatment on oxidative stress and hepatotoxicity in binge ethanol administered rats. Hum Exp Toxicol. 2010; 29(8): 659-65.
  • 18. Kalaz EB, Çoban J, Aydın AF, Doğan Ekici I, Doğru Abbasoğlu S, Öztezcan S, Uysal M. Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by D-galactose in rat liver. J Physiol Biochem. 2014; 70(1): 15-25.
  • 19. Kuloglu N, Sönmez MF. A biochemical and immunohistochemical study of the protective effects of carnosine for carbon tetrachloride induced liver injury in rats. Biotech Histochem. 2015; 90(8): 608-14.
  • 20. Sahin S, Oter S, Burukoğlu D, Sutken E. The effects of carnosine in an experimental rat model of septic shock. Med Sci Monit Basic Res. 2013; 19(7): 54-61.
  • 21. Yan SL, Wu ST, Yin MC, Chen HT, Chen HC. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. J Food Sci. 2009; 74(8): 259-65.
  • 22. Fouad AA, El-Rehany MA, Maghraby HK. The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rat. Eur J Pharmacol. 15; 572(1): 61-8.
  • 23. Baykara B, Tekmen I, Pekcetin C, Ulukus C, Tuncel P, Sagol O, Ormen M, Ozogul C. The protective effects of carnosine and melatonin in ischemia-reperfusion injury in the rat liver. Acta Histochem. 2009; 111(1): 42-51.
  • 24. Başaran Küçükgergin C, Bingül I, Tekkeşin MS, Olgaç V, Doğru Abbasoğlu S, Uysal M. Effects of carnosine, taurine, and betaine pretreatments on diethylnitrosamine-induced oxidative stress and tissue injury in rat liver. Toxicol Ind Health. 2016; 32 (8): 1405-1413
  • 25. Tokyol C, Yilmaz S, Kahraman A, et. al. The effects of desferrioxamine and carnosine on liver injury induced by hepatic ischaemia-reperfusion in rats. Acta Chir Belg. 2006; 106(1): 68- 72.
  • 26. Welker AF, Moreira DC, Hermes-Lima M. Roles of catalase and glutathione peroxidase in the tolerance of a pulmonate gastropod to anoxia and reoxygenation. J Comp Physiol B. 2016; 186(5): 553-68.
  • 27. Prokopieva VD, Yarygina EG, Bokhan NA, Ivanova SA. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies. Oxid Med Cell Longev. 2016;2016:2939087. doi: 10.1155/2016/2939087. Epub 2016 Jan 24.

Protective Effect of Carnosine on Hepatic Ischemia-Reperfusion Injury in Rats

Yıl 2020, Cilt: 42 Sayı: 3, 269 - 276, 27.05.2020
https://doi.org/10.20515/otd.481714

Öz

Karaciğer
iskemi-reperfüzyon uygulanmış ratlarda Karnozinin karaciğer hasarında
antioksidan özelliği ile iyileştirici ve koruyucu etkisinin incelenmesi
amacıyla  bu çalışma planlandı.
Cinsiyetleri erkek olan ağırlıkları
200-250 gr. arasında değişen Sprague-Dawley cinsi 30 adet rat,  10 ar adet
rattan oluşan kontrol  grubu, karaciğer iskemi-reperfüzyon İ/R grubu, ve Karaciğer
İ/R + 100mg/kg Karnozin grubu olmak üzere üç gruba ayrıldı. Sham grubuna sadece
laparatomi yapıldı. Diğer gruplardaki tüm ratlara laparatomi sonrası karaciğere
1 saat iskemi  2 saat reperfüzyon uygulandı. IR + karnozin grubuna 
iskemi öncesi 100 mg/kg karnozin ip verildi. Reperfüzyon sonrası ratlardan
Aspartat transaminaz (AST), Alanin transaminaz (ALT), Katalaz (CAT),
Malondialdehid (MDA) için kan örnekleri, ayrıca Malondialdehid (MDA) için
karaciğer doku örnekleri, histopatolojik inceleme için karaciğer doku örnekleri
alındı. Tedavi gruplarında AST, ALT, MDA (serum) , doku MDA ve katalaz
değerlerinde  tedavi verilmeyen gruba göre anlamlı azalma saptanmıştır.
Karnozinin   histolojik açıdan anlamlı düzelmeler sağladığı göz önüne
alındığında özellikle son yıllarda  artan karaciğer nakli sırasına gelişen
iskemi-reperfüzyon hasarının beraberinde getirdiği komplikasyonlarda ve
mortalitede azalmaya yol açabileceği sonucuna varıldı.

Kaynakça

  • 1. Carden and Granger. Pathophysiology of ischemia-reperfusion injury. Pathol, 2000; 190: 255–266.
  • 2. Teoh NC, Farrell GC. Hepatic ischemia reperfusion injury: pathogenic mechanisms and basis for hepatoprotection. J Gastroenterol Hepatol, 2003; 18: 891–902.
  • 3. Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry and Cell Biology. 2007; 39(1): 44–84. doi: 10.1016/j.biocel.2006.07.001.
  • 4. Golubović S, Stanković I, Ristić L, Cosić V, Dordević I, Radović M. Antioxidant enzymes and lipid peroxidation products in patients with pulmonary tuberculosis. Med Pregl. 2010; 63: 450-3.
  • 5. Abdel-Gaber SA, Ibrahim MA, Amin EF, Ibrahim SA, Mohammed RK, Abdelrahman AM. Effect of selective versus non-selective cyclooxygenase inhibitors on ischemia-reperfusion-induced hepatic injury in rats. Life Sci. 2015; 134(1): 42-8. doi: 10.1016/j.lfs.2015.04.025.
  • 6. Fouad AA, El-RehanyMA, Maghraby HK. The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rats. Eur J Pharmacol. 2007 Oct 15;572(1):61-8. Epub 2007 Jun 15
  • 7. Yamashita S, Sato M, Matsumoto T et al Mechanisms of carnosine-induced activation of neuronal cells. Biosci Biotechnol Biochem. 2017 Dec 11:1-6
  • 8. Sahin S,Burukoglu Donmez D. Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of Acute Kidney Injury Due to Septic Shock. Med Sci Monit. 2018 Jan 15;24:305-316.
  • 9. Jamshidzadeh A, Heidari R, Latifpour Z et al Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats. Clin Res Hepatol Gastroenterol. 2017 Sep;41(4):424-434
  • 10. Qi B, Wang J, Ma YB, Wu SG.Effect of dietary β-alanine supplementation on growth performance, meat quality, carnosinecontent, and gene expression of carnosine-related enzymes in broilers.Poult Sci. 2018 Jan 6. doi: 10.3382/ps/pex410
  • 11. Nakagawa K, Kawagoe M, Yoshimura M, Arata H, Minamikawa T, Nakamura M. Differential effects of flavonoid carnosine on oxidative damages induced by hydrophilic and lipophilic radical generator in hepatic Iysosomal fractions of mice. J. Health Science, 2000; 46: 509-512.
  • 12. Yabe Y, Kobayashi N, Nishihashi T, Takahashi R, Nishikawa M, Takakura Y. et al. Prevention of neutrofil-mediated hepatic ischemia-reperfusion injury by Superoxide dismutase and Catalase derivatives. J. Pharmacol. Exp. Ther. 2001; 298: 894-899.
  • 13. Singh D, Chander V, Chopra K. The effect of carnosine, a bioflavonoid on ischemia/reperfusion induced renal injury in rats. Arch Med Res. 2008; 39(7): 714.
  • 14. Peralta C, Bartrons R, Serafin A, Blazquez C, Guzman M, Prats N. et al. Adenosine Monophosphate–Activated Protein Kinase Mediates the Protective Effects of Ischemic Preconditioning on Hepatic Ischemia-Reperfusion Injury in the Rat. Hepatology. 2001; 34(6): 1164-1173.
  • 15. Cuzzocrea, G. Costantino, E. Mazzon, A. Micali, A. De Sarro, A.P.CaputiBenefical effects of melatonin in a rat model of splanchnic artery occlusion and reperfusion J Pineal Res, 28 (2000), pp. 52-63
  • 16. Fan FY, Huang LZ, Wang GY, Zheng W, Wang B, Zhou H, Wang ZL. Effect of carnosine on prevention of reperfusion liver injury during hemorrhagic shock and reperfusion in rats. Article in Chinese. Zhonghua Gan Zang Bing Za Zhi. 2006; 14(12): 942-3.
  • 17. Artun BC, Küskü Kiraz Z, Güllüoğlu M, Cevikbaş U, Koçak Toker N, Uysal M. The effect of carnosine pretreatment on oxidative stress and hepatotoxicity in binge ethanol administered rats. Hum Exp Toxicol. 2010; 29(8): 659-65.
  • 18. Kalaz EB, Çoban J, Aydın AF, Doğan Ekici I, Doğru Abbasoğlu S, Öztezcan S, Uysal M. Carnosine and taurine treatments decreased oxidative stress and tissue damage induced by D-galactose in rat liver. J Physiol Biochem. 2014; 70(1): 15-25.
  • 19. Kuloglu N, Sönmez MF. A biochemical and immunohistochemical study of the protective effects of carnosine for carbon tetrachloride induced liver injury in rats. Biotech Histochem. 2015; 90(8): 608-14.
  • 20. Sahin S, Oter S, Burukoğlu D, Sutken E. The effects of carnosine in an experimental rat model of septic shock. Med Sci Monit Basic Res. 2013; 19(7): 54-61.
  • 21. Yan SL, Wu ST, Yin MC, Chen HT, Chen HC. Protective effects from carnosine and histidine on acetaminophen-induced liver injury. J Food Sci. 2009; 74(8): 259-65.
  • 22. Fouad AA, El-Rehany MA, Maghraby HK. The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rat. Eur J Pharmacol. 15; 572(1): 61-8.
  • 23. Baykara B, Tekmen I, Pekcetin C, Ulukus C, Tuncel P, Sagol O, Ormen M, Ozogul C. The protective effects of carnosine and melatonin in ischemia-reperfusion injury in the rat liver. Acta Histochem. 2009; 111(1): 42-51.
  • 24. Başaran Küçükgergin C, Bingül I, Tekkeşin MS, Olgaç V, Doğru Abbasoğlu S, Uysal M. Effects of carnosine, taurine, and betaine pretreatments on diethylnitrosamine-induced oxidative stress and tissue injury in rat liver. Toxicol Ind Health. 2016; 32 (8): 1405-1413
  • 25. Tokyol C, Yilmaz S, Kahraman A, et. al. The effects of desferrioxamine and carnosine on liver injury induced by hepatic ischaemia-reperfusion in rats. Acta Chir Belg. 2006; 106(1): 68- 72.
  • 26. Welker AF, Moreira DC, Hermes-Lima M. Roles of catalase and glutathione peroxidase in the tolerance of a pulmonate gastropod to anoxia and reoxygenation. J Comp Physiol B. 2016; 186(5): 553-68.
  • 27. Prokopieva VD, Yarygina EG, Bokhan NA, Ivanova SA. Use of Carnosine for Oxidative Stress Reduction in Different Pathologies. Oxid Med Cell Longev. 2016;2016:2939087. doi: 10.1155/2016/2939087. Epub 2016 Jan 24.
Toplam 27 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm ORİJİNAL MAKALELER / ORIGINAL ARTICLES
Yazarlar

Sabiha Sahin 0000-0003-0759-4158

Ufuk Uylaş Bu kişi benim 0000-0003-0759-4158

Varol Sahinturk Bu kişi benim 0000-0003-0759-4158

Ozkan Alatas Bu kişi benim 0000-0003-0759-4158

Yayımlanma Tarihi 27 Mayıs 2020
Yayımlandığı Sayı Yıl 2020 Cilt: 42 Sayı: 3

Kaynak Göster

Vancouver Sahin S, Uylaş U, Sahinturk V, Alatas O. Protective Effect of Carnosine on Hepatic Ischemia-Reperfusion Injury in Rats. Osmangazi Tıp Dergisi. 2020;42(3):269-76.


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