Urological Research

, Volume 33, Issue 3, pp 239–243 | Cite as

A novel antioxidant agent caffeic acid phenethyl ester prevents shock wave-induced renal tubular oxidative stress

  • Fehmi OzgunerEmail author
  • Abdullah Armagan
  • Ahmet Koyu
  • Sadettin Calıskan
  • Halis Koylu
Original Paper


The aim of this study was to evaluate the effects of the novel free radical scavenger caffeic acid phenethyl ester (CAPE) on extracorporeal shock wave lithotripsy (ESWL) induced renal impairment. The study was performed using 30 rabbits which were divided into two groups, each exposed to 3,000 shock waves at 18 kV: (1) control group, (2) ESWL+CAPE treated group. Malodialdehyde (MDA), urine N-acetyl-β-glucosaminidase (NAG) activity, uric acid and white cell counts were used as markers of oxidative stress. Following shock wave exposure there was a significant rise in MDA, NAG and uric acid and white cell counts. CAPE reduced the rise in MDA, NAG, uric acid and white cell counts. Thus CAPE treatment to a great extent prevented the induction of these renal changes. Our results suggest that the antioxidant capacity of the kidney tissue was reduced after ESWL treatment and that the tissue was exposed to oxidant stress. We conclude that CAPE treatment provided significant protection against ESWL induced free radical damage.


Shock wave induced renal oxidative damage Caffeic acid phenethyl ester 


  1. 1.
    Strohmaier WL, Lahme S, Weidenbach PM, Bichler KH (1999) Reduction of high-energy shock-wave-induced renal tubular injury by selenium. Urol Res 27: 382CrossRefPubMedGoogle Scholar
  2. 2.
    Biri H, Ozturk HS, Buyukkocak S, Kacmaz M, Cimen MY, Unal D, Birey M, Bozkirli I, Durak I (1998) Antioxidant defense potential of rabbit renal tissues after ESWL: protective effects of antioxidant vitamins. Nephron 79: 181CrossRefPubMedGoogle Scholar
  3. 3.
    Morgan TR, Laudone PV, Heston WD, Zeitz L, Fair WR (1988) Free radical production by high energy shock waves comparison with ionising irradiation. J Urol 139: 186PubMedGoogle Scholar
  4. 4.
    Suhr D, Brummer F, Hulcer DF (1991) Cavitation-generated free radicals during shock wave exposure: investigations with cell-free solutions and suspended cells. Ultrasound Med Biol 17: 761CrossRefPubMedGoogle Scholar
  5. 5.
    Kirkali Z, Kirkali G, Tahiri Y (1994) The effect of extracorporeal electromagnetic shock waves on renal proximal tubular function. Int Urol Nephrol 26: 255PubMedGoogle Scholar
  6. 6.
    Crum LA (1988) Cavitation microjets as a contributory mechanism for renal calculus disintegration in ESWL. J Urol 140: 1587PubMedGoogle Scholar
  7. 7.
    Serel TA, Ozguner F, Soyupek S(2004) Prevention of shock wave-induced renal oxidative stress by melatonin: an experimental study. Urol Res 32: 69CrossRefPubMedGoogle Scholar
  8. 8.
    Bosomworth MP, Aparicio SR, Hay AWM (1999) Urine N-acetyl-β-D-glucosaminidase-A marker of tubular damage. Nephrol Dial Transplant 14: 620CrossRefPubMedGoogle Scholar
  9. 9.
    Raab WP (1972) Diagnostic value of urinary enzyme determinations. Clin Chem 18: 5PubMedGoogle Scholar
  10. 10.
    Ilhan A, Koltuksuz U, Ozen S, Uz E, Ciralik H, Akyol O (1999) The effects of caffeic acid phenethyl ester (CAPE) on spinal cord ischemia/reperfusion injury in rabbits. Eur J Cardiothorac Surg 16: 458CrossRefPubMedGoogle Scholar
  11. 11.
    Rao C, Desai D, Kaul B, Amin S, Reddy BS (1992) Effect of caffeic acid esters on carcinogen-induced mutagenicity and human colon adenocarcinoma cell growth. Chem Biol Interact 84: 277CrossRefPubMedGoogle Scholar
  12. 12.
    Sud’ina GF, Mirzoeva OK, Pushkareva GA, Korshunova GA, Sumbatyan NV, Varfolomeev SD (1993) Caffeic acid phenethyl ester as a lipoxygenase inhibitor with antioxidant properties. FEBS Lett 329: 21CrossRefPubMedGoogle Scholar
  13. 13.
    Michaluart P, Masferrer JL, Carothers AM, Subbaramaiah K, Zweifel BS, Koboldt C, Mestre JR, Grunberger D, Sacks PG, Tanabe T, Dannenberg AJ (1999) Inhibitory effects of caffeic acid phenethyl ester on the activity and expression of cyclooxygenase-2 in human oral epithelial cells and in rat model of inflammation. Cancer Res 59: 2347PubMedGoogle Scholar
  14. 14.
    Chen YJ, Shiao MS, Wang SY (2001) The antioxidant caffeic acid phenethyl ester induces apoptosis associated with selective scavenging of hydrogen peroxide in human leukemic HL-60 cells. Anticancer Drugs 12: 143CrossRefPubMedGoogle Scholar
  15. 15.
    Fesen MR, Pommier Y, Leteurtre E, Hiroguchi S, Yung J, Kohn KW (1994) Inhibition of HIV-1 integrase by flavones, caffeic acid phenethyl ester (CAPE) and related compounds. Biochem Pharmacol 48: 595CrossRefPubMedGoogle Scholar
  16. 16.
    Park EH, Kahng JH (1999) Suppressive effects of propolis in rat adjuvant arthritis. Arch Pharm Res 22: 554PubMedGoogle Scholar
  17. 17.
    Hepsen IF, Er H, Cekic O (1999) Topically applied water extract of propolis to suppress corneal neovascularization in rabbits. Ophthalmic Res 31: 426CrossRefPubMedGoogle Scholar
  18. 18.
    Gurel A, Armutcu F, Sahin S, Sogut S, Ozyurt H, Gulec M, Kutlu NO, Akyol O (2004) Protective role of alphatocopherol and caffeic acid phenethyl ester on ischemia-reperfusion injury via nitric oxide and myeloperoxidase in rat kidneys. Clin Chim Acta 339: 33CrossRefPubMedGoogle Scholar
  19. 19.
    Uz E, Sogut S, Sahin S, Var A, Ozyurt H, Gulec M, Akyol O (2002) The protective role of caffeic acid phenethyl ester (CAPE) on testicular tissue after testicular torsion and detorsion. World J Urol 20: 264PubMedGoogle Scholar
  20. 20.
    Yilmaz HR, Uz E, Yucel N, Altuntas I, Ozcelik N (2004) Protective effect of caffeic acid phenethyl ester (CAPE) on lipid peroxidation and antioxidant enzymes in diabetic rat liver. J Biochem Mol Toxicol 18: 234CrossRefPubMedGoogle Scholar
  21. 21.
    Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186: 421PubMedGoogle Scholar
  22. 22.
    Yakata M, Sugita O, Sakai T, Uchiyama K, Wada K (1983) Urinary enzyme determination and its clinical significance. C. Enzyme derived from the kidney epithelium-N acetyl.beta-D-glucosaminidase. 4. Preclinical evaluation of the urinary NAG activity and changes in the renal disease. Rinsho Byori 56: 90Google Scholar
  23. 23.
    Rovin BH, Wurst E, Kohan DE (1990) Production of reactive oxygen species by tubular epithelium in cell culture. Kidney Int 37: 1509PubMedGoogle Scholar
  24. 24.
    Everaert K, Kerckhaert W, Delanghe J, Lameire N, Sturley W, Van de Wiele C, Dierckx RA, Van de Voorde J, Oosterlinck W (1998) Elevated tubular proteinuria, albuminuria and decreased urinary N-acetyl-beta-D-glucosaminidase activity following unilateral total ureteral obstruction in rats. Urol Res 26: 285CrossRefPubMedGoogle Scholar
  25. 25.
    Kunin CM, Chesney RW, Craig WA, England AC, DeAngelis C (1978) Enzymuria as a marker of renal injury and disease: studies of N-acetyl-β-glucosaminidase in the general population and in patients with renal disease. Pediatrics 62: 751PubMedGoogle Scholar
  26. 26.
    Sarica K, Kosar A, Yaman O, Beduk Y, Durak I, Gogus O, Kavukcu M (1996) Evaluation of ischemia after ESWL: detection of free oxygen radical scavenger enzymes in renal parenchyma subjected to high-energy shock waves. Urol Int 57: 221PubMedGoogle Scholar
  27. 27.
    Yaman O, Sarica K, Ozer G, Soygur T, Kutsal O, Yaman LS, Gous O (1996) Protective effect of verapamil on renal tissue during shockwave application in rabbit model. J Endourol 10: 329PubMedGoogle Scholar
  28. 28.
    Sener G, Paskaloglu K, Toklu H, Kapucu C, Ayanoglu-Dulger G, Kacmaz A, Sakarcan A (2004) Melatonin ameliorates chronic renal failure-induced oxidative organ damage in rats. J Pineal Res 36: 232CrossRefPubMedGoogle Scholar
  29. 29.
    Sakamoto W, Kishimoto T, Nakatani T, Ameno Y, Ohyama A, Kamizuru M, Yasumoto R, Maekawa M (1991) Examination of aggravating factors of urinary excretion of N-acetyl-beta-D-glucosaminidase after extracorporeal shock wave lithotripsy. Nephron 58: 20Google Scholar
  30. 30.
    Strohmaier WL, Koch J, Wilbert DM, Bichler KH (1991) Protective effects of verapamil on shock wave induced tubular dysfunction. J Urol150: 27Google Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Fehmi Ozguner
    • 1
    Email author
  • Abdullah Armagan
    • 2
  • Ahmet Koyu
    • 1
  • Sadettin Calıskan
    • 1
  • Halis Koylu
    • 1
  1. 1.Department of PhysiologySchool of MedicineTurkey
  2. 2.Department of UrologySchool of Medicine

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