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2006, Cilt 4, Sayı 2, Sayfa(lar) 065-075
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The Effects of Defibrotide Administration on Antioxidant Status in Heart and Liver Tissues of Rabbits Fed with High Cholesterol Diet
Handan Ak Çelik1, Hikmet Hakan Aydın1, Ceyda Kabaroğlu2, Can Duman3, Ece Onur Aydemir4,Oya Bayındır2
1Ege Üniversitesi Tıp Fakültesi Biyokimya Anabilim Dalı, İzmir
2Ege Üniversitesi Tıp Fakültesi Klinik Biyokimya Bilim Dalı, İzmir
3Kocaeli Üniversitesi Tıp Fakültesi Biyokimya Anabilim Dalı, Kocaeli
4Celal Bayar Üniversitesi Tıp Fakültesi Biyokimya Anabilim Dalı, Manisa
Keywords: Atherosclerosis; defibrotide; malondialdehyde; catalase; glutathione; nitric oxide

Objective: Defibrotide, a polydeoxyribonucleotide, has been found to modulate endothelial cell function and to have an antithrombotic effect on arteries, veins and capillaries. A significant amonut of evidence has been found about the protective role of defibrotide in different models of tissue and organ ischemia. The aim of this study was to evaluate the effects of defibrotide administration in the modulation of lipid peroxidation, antioxidant enzymes, antioxidant thiol compound glutathione and nitric oxide, a vasoactive mediator, following a high cholesterol diet.

Material and Methods: The study involved 40 New Zeeland male rabbits, fed with standard (Groups I and III) and high cholesterol (Groups II and IV) chow. At the begining of the study, animals in Group III and Group IV were allocated to treatment with defibrotide (60 mg/kg/day). After a 10 week period, effects of defibrotide administration was evaluated by measuring serum cholesterol and malondialdehyde, catalase, GSH, NOx, glutathione reductase, and glutathione S-transferase concentrations in heart and liver tissues.

Results: Compared to the baseline values, serum cholesterol concentrations were increased in Groups II and IV, significantly. In Group II, malondialdehyde concentrations were significantly higher with a parallel decrease in catalase activity. Defibrotide treatment in Group IV, compared to Group II, increased the mean heart and liver nitric oxide levels by 3.62 folds (430.8 vs. 118.8 μmol/g wet tissue) and 2.35 folds (595.5 vs. 253.2 mol/g wet tissue), respectively.

Conclusion: Our observations suggest that long term defibrotide therapy can be protective for the tissues by increasing the nitric oxide levels and antioxidant enzymes activities. Our data also imply that atherogenic diet increases malondialdehyde levels and decreases catalase activity.


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