Sıçanlarda Tıkanma Sarılığında Melatonin ve N-Asetilsisteinin Etkileri

Abstract

Amaç: Tıkanma sarılıklı sıçanlarda, koletastazda N–asetilsistein ve melatoninin etkilerini ve karaciğer ve böbrek hasarında koruyucu rollerini araştırmak ve karşılaştırmak amaçlandı. Materyal ve Metod: 48 sıçan çalışma içinkullanıldı. Sıçanlar sham, ana kontrol ve çalışma olarak 3 ana gruba ayrıldı. Daha sonra ana kontrol grubu erken sakrifikasyon grubu ve kontrol grubuna ayrıldı. Çalışma grupları kendi içinde melatonin, N–asetilsistein ve melatonin & N–asetilsistein olmak üzere üç ayrı alt gruba ayrıldı. Çalışma ve kontrol gruplarında laparotomi yapıldı, koledok dönüldü, bağlandı ve kesildi. İşlemden 5 gün sonra erken sakrifikasyon grubunda; kan örnekleri, karaciğer ve böbrek dokuları alındı. Çalışma gruplarında beşinci günden başlayarak 10. güne kadar subkutan olarak melatonin, N–asetilsistein ve melatonin & N–asetilsistein uygulandı, sham ve kontrol gruplarına serum fizyolojik verildi. 10. Günde tüm gruplardan kan örnekleri, karaciğer ve böbrek doku örnekleri alındı. Bulgular: Total bilirübin, AST, ALT, kreatinin seviyeleri sarılıklı sıçanlarda anlamlı olarak yüksekti. 10. günde kontrol gruplarında AST, ALT, total bilirubin, BUN, kreatinin seviyeleri anlamlı olarak yüksekti. Melatonin, N–asetilsistein ve melatonin & N–asetilsistein grupları karşılaştırıldığında tüm biyokimyasal parametrelerin seviyelerinde anlamlı fark saptanmadı. Kontrol grubunda MDA ve NO seviyeleri çalışma grubundan daha yüksek saptandı. Melatonin, N–asetilsistein ve melatonin & N–asetilsistein grupları karşılaştırıldığında MDA ve NO seviyeleri açısından farklılık yoktu. Histopatolojik bulgularda MDA ve NO değerleri ile benzerlik gösteriyordu. Sonuç: Tıkanma sarılıklı sıçanlarda melatonin ve NAC kullanılması karaciğer ve böbrek dokusunda serbest oksijen radikallerinin yarattığı hasardan korur.

Keywords

• melatonin
• n-asetilsistein
• tıkanma sarılığı
• serbest oskijen radikali

The Effects of Melatonin and N-Acetylcysteine on Obstructive Jaundiced Rats

Abstract

Aim: The aim of this experimental study is to investigate the effects of N- acetylcysteine and melatoninin on the cholestasis and their protective effects on liver and renal injury. Materials and Methods: Forty eight rats were used in the study. Rats were divided into three main groups as sham, main control, and study groups. Main control group divided early sacrification group, control group, study group is divided melatonin, N-acetylcysteine and melatonin & N-acetylcysteine groups. In study and control groups, a laparotomy was performed and the common bile duct was ligated and divided. Five days after the first operation, from early sacrification group blood samples, and liver and renal tissues were collected. For study groups from the fifth day to day 10 melatonin, N-acetylcysteine, melatonin & N-acetylcysteine solutions were applied subcutaneous, saline to the sham and control group. At the day ten from the all groups blood samples, and liver tissues and renal tissues were collected. Results: AST, ALT, BUN, creatinine, total bilirubin levels were significantly higher in jaundiced rats than sham group rats. AST, ALT, total bilirubin, BUN, creatinin levels were significantly higher in the control group at the end of day 10. Among the melatonin group, N-acetylcyteine group and melatonin & N-acetylcysteine group all biochemical parametres were not different. Also the values of MDA and NO for control group were higher than study groups. On the other hand, MDA and NO values were not different between the melatonin group, N-acetylcyteine group and melatonin & N- acetylcysteine group at the end study. Histopathologic findings were also similiar as NO and MDA values. Conclusion: Use of melatonin and N-acetylcysteine in obstructive jaundiced rats, prevents damages of free oxygen radicals on liver and renal tissue.

Keywords

• Melatonin
• N-acetylcysteine,
• obstructive jaundice
• free oxigene radicals

References

1. KAYNAKLAR Parola M, Leonarduzzi G, Robino G, et al. On the role of lipid peroxidation in the pathogenesis of liver demage induced by long-standing cholestasis. Free Radical Biol Med. 1996; 20:351–359.
2. Montilla P, Cruz A, Padillo FJ, et al. Melatonin versus vitamin E as protective treatment against oxidative stres after extra-hepatic bile duct ligation in rats. J. Pineal Research. 2001; 31:138–144.
3. Küçük C, Sözüer EM, İkizceli İ. Role of oxygen free radical scavengers in acute renal failure complicating obstructive jaundice. Eur. Surg. Res. 2003; 35:143–47.
4. Halim AB. Biochemical effect of antioxidants on lipid and liver function in experimentally-induced liver demage. Ann Clin Biochem. 1997; 34: 656–663.
5. Hu C, Zhao L, Tao J, Li L. Protective role of melatonin in early-stage and end-stage liver cirrhosis. J Cell Mol Med. 2019 Nov;23(11):7151-7162.
6. Ballı E. Melatoninin Fonksiyonları. Mersin Üniversitesi Tıp Fak. Dergisi. 2003; 4:380–385.
7. Pazar A, Kolgazi M, Memisoglu A, Bahadir E, Sirvanci S, Yaman A, Yeğen BÇ, Ozek E. The neuroprotective and anti-apoptotic effects of melatonin on hemolytic hyperbilirubinemia-induced oxidative brain damage. J Pineal Res. 2016 Jan;60(1):74-83. Tan DX, Chen LD, Poeggeler B, et al. Melatonin: a potent endogenous hydroxyl radical scavenger. Endocr J. 1993; 1:57–60.
8. Tan DX, Poeggeler B, Reiter RJ, et al. The pineal hormone melatonin inhibits DNA adduct formation induced by the chemical carcinogen role in vivo. Cancer Lett 1993; 70:63–71.

9. Zafarullah M, Li WQ, Sylvester J, et al. Molecular mechanisms of
N–actylysteine actions. Cell Mol. Life Science 2003; 60:6–20.
10. Dülger H, Durmuş A, Sezgi C. KOAH akut atak tedavisinde antioksidan olarak N–asetilsistein’in etkinliği Van Tıp Dergisi. 2002; 9(3): 91–94.
11. Chen C, Shiesh S, Tsao HC, et al. Protective effect of melatonin on renal injury of rats induced by bile ligation. Digestive Diseases and Science. 2001; 46: 927–931.
12. Bülbüller N, Akkuş MA, Çetinkaya Z. Effects of melatonin and lactulose on the liver kidneys in rats with obstructive jaundice. Pediatr Surg Int. 2002; 18: 678–680.
13. Tsai LY, Lee KT, Lu FJ. Biochemical events associated with ligation of the common bile duct in Wistar rats. J Formos Med Assoc 1997; 96:17–22.
14. Deitch EA, Sitting K, Li M, et al. Obtructive jaundive promotes bacterial translocation from gut. Am J Surg 1990; 159:79–84.
15. Gümüs M, Tekin R, Firat U, Onder A, Kapan M, Böyük A, Aldemir M, Kilinç C. The effects of pomegranate on bacterial translocation in rats with obstructive jaundice. Eur Rev Med Pharmacol Sci. 2013 Jun;17(11):1488-94.
16. Bomzon A. Bile acids, oxidative stress and renal function in biliary obstruction Semin Nephro. 1997; 17: 549–562 (Review).
17. Eşrefoğlu M, Gül M, Emre MH. Protective effect of low dose of melatonin against cholestatic oxidative stress after common bile duct ligation in rats. World J Gastroenterol. 2005; 11:1951–1956.
18. Andreadau I, Ilıodromıtıs EK, Mikros E, et al. Melatonin does not prevent the protection of ischemic preconditioning in vivo despite its antioxidant effect against oxidative stres. Free Radic Biol Med. 2004; 37:500–510.
19. Aydoğdu N, Kaymak K,Yalçın Ö. Sıçanlarda Böbrek iskemi/reperfüzyon hasarında N–asetilsisteinin etkileri. Fırat Tıp Dergisi 2005; 10: 151–155.
20. Ommati MM, Amjadinia A, Mousavi K, Azarpira N, Jamshidzadeh A, Heidari R. N-acetyl cysteine treatment mitigates biomarkers of oxidative stress in different tissues of bile duct ligated rats. Stress. 2021 Mar;24(2):213-228.
21. Cotran RS, Kumar V, Collis T ( Eds). Robbins Pathologic Basis Disease (6th ed). WB Saunders Company, Philadelphia 1999; pp 100–101.