ERCAN YUVANÇ, DEVRİM TUĞLU, ÜÇLER KISA, Önder BOZDOĞAN, BÜLENT BAKAR, Ertan BATİSLAM, ERDAL YILMAZ

DENEYSEL TEK TARAFLI ÜRETER OBSTRÜKSİYONU OLUŞTURULAN RATLARDA DİMETİLSÜLFOKSİT VE PİRASETAM’IN BÖBREK HASARINA ETKİSİ

Amaç: Dimetil Sülfoksit (DMSO) ve Pirasetam’ın deneysel unilateral üreter obstrüksiyonu (UÜO) oluşturulan ratlarda böbrek hasarını azaltıcı etkilerinin incelenmesi.Gereç ve Yöntem: Çalışma her biri 6 Sprague-Dawley rattan oluşan 4 deney grubunda yürütüldü. Grup 1: sham, Grup 2: UÜO (kontrol grubu), Grup 3: UÜO + DMSO 3.8 g/kg grubu, Grup 4: UUO + Piracetam 500 mg/kg grubu olarak tanımlandı. Total antioksidan kapasite (TAK) ve total oksidan seviye (TOS) ölçümleri ve histopatolojik inceleme için doku ve kan örnekleri alındı. Doku örnekleri histopatolojik olarak da incelendi.Bulgular: Biyokimyasal ve histopatolojik böbrek hasarı incelendi. Doku Total Antioksidan Kapasite (TAK) düzeyleri değerlendirildiğinde Grup 1 ve Grup 2’ye göre Grup 3 ve 4’de istatiksel olarak anlamlı bir artış olduğu görüldü. Grup 3 ve Grup 4 arasında ise istatiksel olarak anlamlı bir artış olduğu saptandı (p<0.001). Doku Total Oksidan Seviye (TOS) değerleri incelendiğinde Grup 1 ve Grup 2’ye göre Grup 3 ve Grup 4’de oksidan düzeyinde istatiksel olarak anlamlı bir azalma olduğu; aynı zamanda Grup 3 ve Grup 4 arasında da istatiksel olarak anlamlı bir azalma olduğu saptandı (p<0.001). Doku Oksidatif Stres Indeksi (OSI) parametresi incelendiğinde Grup 1 ve Grup 2’ye göre Grup 3 ve 4’de OSI değerlerinde istatiksel olarak anlamlı bir azalma olduğu tespit edildi. Histopatolojik inceleme de böbrek dokusunda Grup 2’ye göre Grup 3 ve 4’te histopatolojik olarak istatistiksel olarak bir fark saptanmadı. Sonuç: Dokuda biyokimyasal düzeyde DMSO ve Pirasetam’ın antioksidan etkili olduğu aynı etkinin histolojik olarak koruyucu etkinlik oluşturmadığı saptanmıştır. Bununla birlikte bu ilaçların farklı doz ve sürelerle yapılacak çalışmalar ile doku antioksidan özelliklerinin saptanabileceği düşünülmektedir.

Anahtar Kelimeler:

Dimetil sülfoksit, pirasetam, oksidatif stres, üreter obstrüksiyonu

The Effect of Dimethyl Sulfoxide and Pyracetam on Kidney Damage in the Rats of Experimental Unilateral Ureteral Obstruction

Objective: The aim of this study was to investigate the effects of Dimethyl Sulfoxide (DMSO) and Piracetam on experimental renal injury in a rat model of unilateral uretheral obstruction (UUO).Material and Methods: A total of 24 Sprague-Dawley rats were divided into 4 groups with 6 rats each as Group 1: sham group, Group 2: UUO (control group), Group 3: UUO + DMSO 3.8 g/kg, Group 4: UUO + Piracetam 500 mg/kg. Total antioxidant capacity (TAC), and total oxidant statüs (TOS) were analyzed biochemically in tissue and blood samples. Tissue samples were also examined histopathologically.Results: Biochemical and histopathological renal injury were evaluated. When the tissue total antioxidant capacity was measured, there was a statistically significant increase in Group 3 and 4 compared to Group 1 and Group 2. There was a statistically significant increase (p <0.001) between Group 3 and Group 4. When the tissue total oxidant status was examined, the oxidant level in Group 3 and Group 4 was significantly decreased compared to Group 1 and Group 2. Also, there was a significant decrease between Group 3 and Group 4. A statistically significant decrease in OSI values was observed in Group 3 and 4 when compared to Group 1 and Group 2. Histopathologic examination showed no significant difference in Group 3 and 4 when compared with Group 2 in kidney tissue. Conclusion: Antioxidant effects of DMSO and piracetam were determined on biochemical level of tissue. However, it has not been found to be protective histologically. Therefore, it is thought that antioxidant properties of tissues can be determined by studies to be performed with different doses and durations of these drugs.

Keywords:

Ureter Obstruction Dimethyl sulphoxide, Pyacetam, Oxidative Stress, Antioxidation,

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Moosavi SM, Ashtiyani SC, Hosseinkhani S, Shirazi M. Comparison of the effects of L-carnitine and alpha-tocopherol on acute ureteral obstruction-induced renal oxidative imbalance and altered energy metabolism in rats. Urol Res. 2010;38:187-94.
Felsen D, Loo MH, Vaughan ED Jr. Effect of ureteral obstruction on renal hemodynamics. Semin Urol. 1987;5:160-6.
Fink RL, Caridis DT, Chmiel R, Ryan G. Renal impairment and its reversibility following variable periods of complete ureteric obstruction. Aust N Z J Surg. 1980;50:77-83.
Naito Y, Yoshikawa T, Yoshida N, Kondo M. Role of oxygen radical and lipid peroxidation in indomethacin-induced gastric mucosal injury. Dig Dis Sci. 1998;43:30-4.
Anderson D. Antioxidant defences against reactive oxygen species causing genetic and other damage. Mutat Res. 1996;350:103-8.
Grollman AP, Moriya M. Mutagenesis by 8-oxoguanine: an enemy within. Trends Genet. 1993;9:246-9.
Tortiglione A, Minale M, Pignataro G, Amoroso S, DiRenzo G, Annunziato L. The 2-oxopyrrolidinacetamid piracetam reduces infarct brain volume induced by permanent middle cerebral artery occlusion in male rats. Neuropharmacology. 2002;43:427-33.
Rameis H, Hitzenberger G, Kutscher R, Manigley C. Pharmacokinetics of piracetam: a study on the bioavailability with special regard to renal and non-renal elimination. Int J Clin Pharmacol Ther. 1994;32(9):458-65. Gabryel B, Adamek M, Pudełko A, Małecki A, Trzeciak HI. Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxygenation. Neurotoxicology. 2002;23(1):19-31.
Gukasov VM, Rasulov MM, Efuni SN, Kaplan EIa, Smiriagina VI. Characteristics of the antihypoxic action of piracetam. Biull Eksp Biol Med. 1987;103(6):683-5.
Ertok E, Guven H, Erman M. Effect of piracetam on postoperative time of recovery in elderly. The Medical Journal of Akdeniz University. 1995;12:1300-9.
Rowe EL, White NA. Reperfusion injury in the equine intestine. Clin Tech Equine Pract. 2002;1:148-62.
Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem. 2004;37:112-9.
Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005; 38: 1103-11.
Claesson G, Svensson L, Robertson B, Josephson S, Cederlund T. Experimental obstructive hydronephrosis in newborn rats. A one-year follow-up study of renal function and morphology. J Urol. 1989;142:1602-7.
Capelouto CC, Saltzman B. The pathophysiology of ureteral obstruction. J Endourol. 1993;7:93-103.
Gillenwater JY. The pathophysiology of urinary tract obstruction. In: Walsh PC, Retik AB, Stamey TA, Vaughn Jr ED, editors. Campbell’s urology. 8th ed. Philadelphia: WB Saunders, 2002:499-505.
Klahr S, Morrissey J. Obstructive nephropathy and renal fibrosis: the role of bone morphogenic protein-7 and hepatocyte growth factor. Kidney Int Suppl. 2003;87:105-12.
Ransley PG, Risdon RA. Renal papillae and intrarenal reflux in the pig. Lancet. 1974;2:1114.
Huland H, Leichtweiss HP, Augustin HJ. Changes in renal hemodynamics in experimental hydronephrosis. Invest Urol. 1981;18:274-7.
Cotran RS, Kumar V, Robbins SL. Robbins pathologic basis of disease. 4th ed. Philadelphia: WB Saunders. 1995: 3-12.
Lu JM, Lin PH, Yao Q, Chen C. Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. J Cell Mol Med. 2010;14:840-60.
Young MR, Young IS, Johnston SR, Rowlands BJ. Lipid peroxidation assessment of free radical production following release of obstructive uropathy. J Urol. 1996;156:1828-32.
Chevalier RL, Chung KH, Smith CD, Ficenec M, Gomez RA. Renal apoptosis and clusterin following ureteral obstruction: the role of maturation. J Urol. 1996;156:1474-9.
Yasar A, Erdemir F, Parlaktas BS, Atilgan D, Koseoglu RD, Saylan O, et al. The effect of carvedilol on serum and tissue oxidative stress parameters in partial ureteral obstruction induced rat model. Kaohsiung Journal of Medical Sciences. 2013;29:19-25.
Brayton CF. Dimethyl sulfoxide (DMSO): a review. Cornell Vet. 1986;76(1):61-90. Santos NC, Figueira-Coelho J, Martins-Silva J, Saldanha C. Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol. 2003;65:1035-41.
Reilly PM, Schiller HJ, Bulkley GB. Pharmacologic approach to tissue injury mediated by free radicals and other reactive oxygen metabolites. Am J Surg. 1991;161(4):488-503.
Bulger EM, Maier RV. Antioxidants in critical illness. Arch Surg. 2001;136:1201-7.
Köksal C, Bozkurt AK, Cangel U, Ustundag N, Konukoglu D, Musellim N, et al. Attenuation of ischemia/reperfusion injury by n-acetylcysteine in a rat hind limb model. J Surg Res. 2003;111:236-9.
Stockmans F, Deberdt W, Nystrom A. Inhibitor effect of piracetam on platelet-rich thrombus formation in an animal model. Thromb Haemost. 1998;79:222-7.
Grassler J, Wustmann C, Fischer HD, Schmidt J, Scheuch DW. Inhibition of stimulated dopamine release from striatum slices after hemorrhagic shock in the rat. Protective effect of piracetam. Meth and Find Exptl Clin Pharmacol. 1987;9:489-91.
Tuncer S, Ayhan S, Findikcioglu K, Ergun H, Tuncer I. Effect of systemic piracetam treatment on flap survival and vascular endothelial growth factor expression after ischemia-reperfusion injury. J Reconstr Microsurg. 2011;27:409-18.