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

Year 2018, Volume: 20 Issue: 1, 18 - 25, 30.04.2018

Ercan Yuvanç , Devrim Tuğlu , Üçler Kısa Önder Bozdoğan , Bülent Bakar , Ertan Batislam Erdal Yılmaz

https://doi.org/10.24938/kutfd.338599

Abstract

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

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

Abstract

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.

Keywords

Dimetil sülfoksit, pirasetam, oksidatif stres, üreter obstrüksiyonu

References

• 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.