Buradasınız

Anasayfa » Content

Sıçanlarda Böbrek İskemi/Reperfüzyon Hasarında N- Asetilsisteinin Etkileri

Effects of N-Acetylcysteine in Renal Ischemia/Reperfusion Injury in the Rats

Journal Name:

  • Fırat Tıp Dergisi

Publication Year:

  • 2005

Key Words:

Keywords (Original Language):

Author NameUniversity of AuthorFaculty of Author
Abstract (2. Language): 
Objectives: Free radicals have played an important role in the pathophysiology of severel disease including renal ischemia/reperfusion injury. The aim of this study was to estimate any protective effects of N-acetylcysteine, an antioxidant and the precursor of glutathione synthesis on the tissue damage during ischemia/reperfusion injury of kidney. Materials and Methods: Twenty four female Spraque Dawley rats divided into three groups: Group 1; was given saline intraperitonealy. Group 2; subjected to bilateral renal ischemia followed by reperfusion and saline injected ip 30 min before induction of ischemia. Group 3; is also subjected to bilateral renal ischemia followed by reperfusion and N-acetylcysteine (300 mg/kg) injected intraperitonealy 30 min before induction of ischemia. At the end of the reperfusion period, the rats were sacrificed. Kidney superoxide dismutase, catalase, glutathione peroxidase activities, malondialdehyde and glutathione levels, plasma urea, creatinine, glutathione and malondialdehyde levels were determined. Kidney was also histopathologically examined. Results: İschemia/reperfusion application was increased urea and creatinin levels (p<0.001), it decreased "superoxide dismutase (p<0.01), catalase". Both plasma and kidney malondialdehyde levels were increased and glutathione levels were decreased. In this group, necrosis and cast formation were also increased. N-acetylcysteine application was decreased malondialdehyde levels in both plasma and kidney tissue (p<0.001), and increased glutathione levels. Histopathological findings has shown a significant decrease in necrosis (p<0.05) and cast formation (p<0.01). Conclusion: In the kidney ischemia/reperfusion injury, the oxidative stress may play an important role and application of N-acetylcysteine may improve tissue damage. ©2005, Fırat Üniversitesi, Tıp Fakültesi
Bookmark/Search this post with
Abstract (Original Language): 
Amaç: Serbest radikaller, böbrek iskemi/reperfüzyon hasarı gibi birçok hastalığın patofizyolojisinde önemli rol oynarlar. Çalışmamızda, antioksidan ve glutatyonun öncüsü olan N-asetilsisteinin iskemi/reperfüzyonun böbreklerde oluşturduğu hasara karşı iyileştirici etkisinin olup olmadığını araştırmayı amaçladık. Gereç ve Yöntem: 24 adet dişi Sprague Dawley sıçan, 1. grup kontrol grubu, 2. grup İ/R grubu, 3. grup İ/R+NAC grubu olmak üzere, eşit sayıda 3 gruba ayrıldı. Kontrol grubuna intraperitoneal serum fizyolojik verildi. İ/R ve İ/R+NAC gruplarında, ksilazin-ketamin anestezisi altında her iki böbrek damarları klemp aracılığı ile kapatılarak, 60 dakika (dk) iskemi ve 24 saat reperfüzyon uygulandı. İskemiden 30 dk önce İ/R grubuna fizyolojik serum, İ/R+NAC grubuna 300 mg/kg N-asetilsistein intraperitoneal verildi. Kontrol grubunun fizyolojik serum enjeksiyonundan 24 saat sonra, İ/R ve İ/R+NAC gruplarının reperfüzyon döneminden sonra ksilazin-ketamin anestezisi altında kan örneği ve böbrek dokuları alındı. Böbrek dokusu süperoksit dismutaz, katalaz, glutatyon peroksidaz enzim aktiviteleri ile glutatyon ve malondialdehit düzeyleri; plazma üre, kreatinin, glutatyon ve malondialdehit düzeyleri belirlendi. Ayrıca böbrek dokusu histopatolojik olarak incelendi. Bulgular: İskemi/reperfüzyon grubunda; üre ve kreatinin düzeylerinin arttığı (p<0.001), süperoksit dismutaz (p<0.01), katalaz ve glutatyon peroksidaz (p<0.001) aktivitelerinin azaldığı görülmüştür. Hem böbreklerde hem de plazmada malondialdehit düzeyinin arttığı, glutatyon düzeyinin azaldığı, histopatolojik incelemede ise nekroz ve kast bulgularında artma izlenmiştir. N-asetilsistein uygulanan grupta, hem plazma hem de böbrek malondialdehit düzeyinde azalma (p<0.001) ve glutatyon (plazma p<0.001; böbrek p<0.01) düzeyinde artış elde edilmiştir. Böbreklerin histopatolojik incelenmesinde nekroz (p<0.05) ve kast (p<0.01) bulgularında azalma tespit edilmiştir. Sonuç: Böbrek İ/R hasarında oksidatif stresin önemli rol oynadığı ve bu hasara karşı N-asetilsistein verilmesinin koruyucu rol oynadığı görüldü. ©2005, Fırat Üniversitesi, Tıp Fakültes
FULL TEXT (PDF): 
PDF icon reperfuzyon-hasarinda-n-asetilsisteinin-etkileri.pdf
  • 4
151-155
  • Turkish

REFERENCES

References: 

1.
Cones
a LE, Valero F, Nadal JC ve ark.. N-acetyl-L-cysteine improves renal medullary hypoperfusion in acute renal failure.
Am J Physiol 2001; 281: R730-R737.
2. Laurent B, Ardaillou R. Reactive oxygen species: production and
role in the kidney. Am J Physiol 1986; 251: F765-F776.
3. Nath KA, Norby SM. Reactive oxygen species and acute renal
failure. Am J Med 2000; 109: 655-678.
4. Paller MS, Hoidal JR, Ferris TF. Oxygen free radicals in ischemic acute renal failure in rat. J Clin İnvest 1984; 74: 1156-1164.
5. Paller MS. The cell biology of reperfusion injury in the kidney. J
Invest Med 1994; 42: 632-639.
6. Dobashi K, Ghosh B, Orak JK, Singh I, Singh AK. Kidney
ischemia-reperfusion: Modulation of antioxidant defenses. Mol Cell Biochem 2000; 205: 1-11.
7. Meister A, Anderson ME. Glutathione. Annu Rev Biochem 1983; 52: 711-760.
8. Slusser SO, Grotyohann
LW
, Martin LF, Scaduto RC. Glutathione catabolism by the ischemic rat kidney. Am J Physiol
1990; 258(6): F1546-F1553.
9. Sehirli AO, Sener G, Satiroglu H, Ayanoglu-Dulger G. Protective effect of N-acetylcysteine on renal ischemia/reperfusion injury in
the rat. J Nephrol 2003; 16(1): 75-80.
10. Abbasoğlu SD, Balkan J, Kanbağlı Ö ve ark.. Aminoguanidin ve N-asetilsisteinin endotoksemik sirozlu sıçanlarda karaciğer hasarı, oksidatif ve nitrozatif stres üzerine etkisi. Kocatepe Tıp
Dergisi 2004; 5(1): 27-32.
11. Tariq M, Morais C, Sobki S ve ark.. N-acetylcysteine attanuates cyclosporine-induced nephrotoxicity in rats. Nephrol Dial
Transplant 1999; 14: 923-929.
12. Ishizuka S, Nagashima Y, Numata M ve ark.. Regulation and immunohistochemical analysis of stress protein heme oxygenase-
154
Fırat Tıp Dergisi 2005;10(4): 151-155
1 in rat kidney mith myoglobinuric acute renal failure. Bioc Biop
Res Com1997; 240: 93-98.
13. Shaikh ZA, Zaman K, Tang W, Vu T. Treatment of chronic cadmium nephrotoxicity by N-acetylcysteine. Toxicology Lett 1999; 104: 137-142.
14. Erdem A, Gündoğan GÜ, Usubütün A ve ark. The antioxidant action of N-acetylcysteine on gentamicin-induced acute tubuler necrosis in rats. Gazi Medical Journal 1999; 10: 21-28.
15. Pincemail J, Defraigne JO, Detry O ve ark.. Ischemia-reperfusion injury of rabbit kidney: comparative effects of desferrioxamine and N-acetylcysteine as antioxidants.Transplant Proc 2000; 32:
475-476.
16. Dimari J, Megyesi J, Udvarhelyi N ve ark.. N-acetyl cysteine ameliorates ischemic renal failure. Am J Physiol 1997; 272:F292-
98.
17. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of
superoxide dismutase. Clin Chem 1988; 34: 497-500.
18. Aebi H. Catalase invitro assay methods. Methods Enzymol 1984;
105: 121-126.
19. Lawrance RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Com 1976;
71: 952-958.
20. Lowry OH, Rosebrough NJ, Farr AL, Randall RI. Protein measurement with the folin phenol reagent. J Biol Chem 1951;
193: 265-275.
Aydoğdu
v
e Ark.
21. Ohkawa H, Ohishi N, Yagi K. Assay for lipit peroxides in animal tissues by thiobarbutiric acid reaction. Anal Biochem 1979; 95:
351-358.
22. Elman GL. Tissue sulfhydryl groups. Arch Biochem Biophys
1959; 82: 70-77.
23. Weinberg JM, Nissim I, Roeser NF ve ark.. Relationships between intracellular amino acid levels and protection against injury to isolated proximal tubules. Am J Physiol Renal Fluid
Electrolyte Physiol 1991; 260: F410-F419.
24. Scaduto RC, Martin VH. Elevation of renal glutathione enhances ischemic injury. Renal Physiol Biochem 1991; 14: 59-70.
25. Erbas H, Aydogdu N, Kaymak K. Effects of N-acetylcysteine on arginase, ornithine and nitric oxide in renal ischemia-reperfusion
injury. Pharmacol Res 2004; 50: 523-527.
26. Mandel LJ, Schnellmann RG, William RJ. Intracellular glutathione in the protection from anoxic injury in renal proximal tubules. J Clin Invest 1989; 85: 316-324.
27. Paller MS. Renal work, glutathione and susceptibility to free radical-mediated postischemic injury. Kidney Int 1988; 33: 843¬849.
28. Cuzzocrea S, Mazzon E, Costantino G ve ark.. Effects of N-acetylcysteine in a rat model of ischemia and reperfusion injury.
Cardiovasc Res 2000; 47: 537-548.

Thank you for copying data from http://www.arastirmax.com