This study investigated the antioxidant effects of carnosine (CAR) in rats exposed to hepatic ischemia-reperfusion (I/R) injury using biochemical and histopathological evaluation. Twenty-four Sprague-Dawley male rats weighing 200–250 g were used to investigate the antioxidant effects of carnosine on the liver. Rats were randomly divided into the following groups: sham (control) group (G1), hepatic I/R group (G2), and hepatic I/R treated with 100 mg/kg CAR group (G3). Rats in the control group underwent only laparotomy and catheterisation. Rats in the other groups received 2 h of reperfusion following 1 h of hepatic ischemia by hepatic artery clamping after laparotomy. Rats in the treatment group received an intraperitoneal (i.p.) injection of 100 mg/kg CAR 60 min before hepatic artery clamping. All rats were monitored for 48 h. Then, they were sacrificed and blood samples were obtained for determination of aspartate transaminase (AST), alanine transaminase (ALT), and liver tissue samples were taken for malondialdehyde (MDA), glutathione (GSH) and catalase (CAT) levels, and for the histopathologic examination as well. Serum AST, ALT and tissue MDA levels were significantly decreased and GSH and CAT levels were significantly higher in the CARtreated group compared to the non-treated group exposed to only I/R injury. Histopathological damage was significantly less in rats which received carnosine than that of non-treated group. We concluded that 100 mg/kg CAR may be effective in preventing the oxidative damage in liver tissue due to I/R injury.
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.
___
1. 1.Carden DL, Granger DN. Pathophysiology of ischemia-reperfusion injury. Pathol. 2000;190:255-66.
2. Teoh NC, Farrell GC. Hepatic ischemiareperfusion 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. Int J Biochem Cell Biol. 2007;39(1):44-84.
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 ischemiareperfusion-induced hepatic injury in rats. Life Sci. 2015;134:42-8.
6. Fouad AA,El-Rehany MA,Maghraby HK. The hepatoprotective effect of carnosine against ischemia/reperfusion liver injury in rats. Eur J Pharmacol. 2007;572:61-8.
7. Yamashita S, Sato M, Matsumoto T. Mechanisms of carnosine-induced activation of neuronal cells. Biosci Biotechnol Biochem. 2017;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;24:305-16.
9. Jamshidzadeh A, Heidari R, Latifpour Z Carnosine ameliorates liver fibrosis and hyperammonemia in cirrhotic rats. Clin Res Hepatol Gastroenterol. 2017;41:424-34.
10. Qi B, Wang J, Ma YB, Wu SG. Effect of dietary β-alanine supplementation on growth performance, meat quality, carnosine content, and gene expression of carnosine-related enzymes in broilers. Poult Sci. 2018;97:1220- 28.
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 lysosomal fractions of mice. J Health Science. 2000;46:509-12.
12. Peralta C, Bartrons R, Serafin A, Blazquez C, Guzman M, Prats N. Adenosine monophosphate–activated protein kinase mediates the protective effects of ischemic preconditioning on hepatic ischemiareperfusion injury in the rat. Hepatology. 2001;34:1164-73.
13. Aydın AF, Bingül İ, Küçükgergin C, DoğanEkici I, Doğru Abbasoğlu S, Uysal M.Carnosine decreased oxidation and glycation products in serum and liver of highfat diet and low-dose streptozotocin-induced diabetic rats.Int J Exp Pathol. 2017;98:278-88.
14. Schroeter R, Lankisch PG, Lege L, Vogt W. Possible implication of glutathione reductase in haemolysis by the direct lytic factor of cobra venom (Naja naja). Naunyn Schmiedebergs Arch Pharmacol. 1972;275:203-11.
15. Yabe Y, Kobayashi N, Nishihashi T, Takahashi R, Nishikawa M, Takakura Y. Prevention of neutrofil-mediated hepatic ischemia-reperfusion injury by superoxide dismutase and catalase derivatives. Journal of Pharmacology and Experimental Therapy. 2001;298:894-99.
16. Singh D, Chander V, Chopra K. The effect of carnosine, a bioflavonoid on ischemia/reperfusion induced renal injury in rats. Arch Med Res. 2008;39:714.
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;29:659-65
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;70:15-25.
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;90:608-14.
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;19:54-61.
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;74:259-65.
22. 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;111:42-51.
23. 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;32:1405-13.
24. Bingül İ, Yılmaz Z, Aydın AF, Çoban J, Doğru-Abbasoğlu S, Uysal M1.Antiglycation and anti-oxidant efficiency of carnosine in the plasma and liver of aged rats.Geriatr Gerontol Int. 2017;17:2610-14.
25. 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: 553-68.
26. 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.