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Citrate and vitamin E blunt the shock wave-induced free radical surge in an in vitro cell culture model

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Abstract

Free radical formation plays a major role in shock wave lithotripsy induced renal damage. Moreover, previous studies suggest that free radicals may also promote de novo calcium oxalate crystallization of previously damaged urothelium. Citrate is a known inhibitor of renal stone formation and has also been used as a free radical scavenger. Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we investigated the influence of two free radical scavengers, citrate and vitamin E, on the prevention of the shock wave-induced free radical surge. Suspensions of MDCK cells were placed in containers for shock wave exposure. Six groups of six containers each were examined: (a) no scavengers 0 shocks, (b) no scavengers 100 shocks, (c) citrate 0 shocks, (d) citrate 100 shocks, (e) vitamin E 0 shocks, (f) vitamin E 100 shocks. An unmodified HM3 was used to deliver 100 shocks at 24 kV. The cell groups that were not shocked acted as the control group and were handled identically, except for the lack of shock wave exposure. After shock wave administration, the containers were emptied and cell suspensions were immediately centrifuged. The supernatant was examined for lactate dehydrogenase (LDH) and 8-isoprostane (8-IP), markers of cellular injury and free radical formation, respectively. Intracellular LDH uniformly increased in all groups exposed to shock wave energy. Similarly, 8-IP increased in all shocked groups. However, the 8-IP increase was significantly reduced when the free radical scavengers were employed. As citrate is a well-known inhibitor of calcium nephrolithiasis, its mechanism of action may be further enhanced, based on its ability to reduce free radical formation, by a protective effect on the urothelium. These data further support the use of citrate based medications during the peri-operative period of shock wave lithotripsy, not only to inhibit stone formation and facilitate fragment passage, but also to reduce the incidence of shock wave induced renal damage. Further studies are warranted to clinically test this hypothesis.

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References

  1. Burton KP, Morris AC, Massey KD, Buja LM, Hagler HK (1990) Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. J Mol Cell Cardiol 22: 1035

    Article  PubMed  Google Scholar 

  2. Rovin BH, Wurst E, Kohan DE (1990) Production of reactive oxygen species by tubular epithelial cells in culture. Kidney Int 37: 1509

    PubMed  Google Scholar 

  3. Morgan TR, Laudone VP, Heston WD, Zeitz L, Fair WR (1988) Free radical production by high energy shock waves—comparison with ionizing irradiation. J Urol 139: 186

    PubMed  Google Scholar 

  4. Suhr D, Brummer F, Hulser DF (1991) Cavitation-generated free radicals during shock wave exposure: investigations with cell-free solutions and suspended cells. Ultrasound Med Biol 17: 761

    Article  PubMed  Google Scholar 

  5. Thamilselvan S, Khan SR, Menon M (2003) Oxalate and calcium oxalate mediated free radical toxicity in renal epithelial cells: effect of antioxidants. Urol Res 31: 3

    PubMed  Google Scholar 

  6. Thamilselvan S, Khan SR (1998) Oxalate and calcium oxalate crystals are injurious to renal epithelial cells: results of in vivo and in vitro studies. J Nephrol 11 [Suppl 1]: 66

    Google Scholar 

  7. Scheid C, Koul H, Hill WA, Luber-Narod J, Jonassen J, Honeyman T, Kennington L, Kohli R, Hodapp J, Ayvazian P, Menon M (1996) Oxalate toxicity in LLC-PK1 cells, a line of renal epithelial cells. J Urol 155: 1112

    Article  PubMed  Google Scholar 

  8. Scheid CR, Koul HK, Kennington L, Hill WA, Luber-Narod J, Jonassen J, Honeyman T, Menon M (1995) Oxalate-induced damage to renal tubular cells. Scanning Microsc 9: 1097

    PubMed  Google Scholar 

  9. Scheid C, Koul H, Hill WA, Luber-Narod J, Kennington L, Honeyman T, Jonassen J, Menon M (1996) Oxalate toxicity in LLC-PK1 cells: role of free radicals. Kidney Int 49: 413

    PubMed  Google Scholar 

  10. Strohmaier WL, Bichler KH, Deetjen P, Kleinknecht S, Pedro M, Wilbert D (1990) Damaging effects of high energy shock waves on cultured Madin-Darby canine kidney (MDCK) cells. Urol Res 18: 255

    Article  PubMed  Google Scholar 

  11. Willis LR, Evan AP, Connors BA, Fineberg NS, Lingeman JE (1997) Effects of SWL on glomerular filtration rate and renal plasma flow in uninephrectomized minipigs. J Endourol 11: 27

    PubMed  Google Scholar 

  12. Delvecchio F, Auge BK, Munver R, Brown SA, Brizuela R, Zhong P, Preminger GM (2003) Shock wave lithotripsy causes ipsilateral renal injury remote from the focal point: the role of regional vasoconstriction. J Urol 169: 1526

    Article  PubMed  Google Scholar 

  13. Brown SA, Munver R, Delvecchio FC, Kuo RL, Zhong P, Preminger GM (2000) Microdialysis assessment of shock wave lithotripsy-induced renal injury. Urology 56: 364

    Article  PubMed  Google Scholar 

  14. Munver R, Delvecchio FC, Kuo RL, Brown SA, Zhong P, Preminger GM (2002) In vivo assessment of free radical activity during shock wave lithotripsy using a microdialysis system: the renoprotective action of allopurinol. J Urol 167: 327

    Article  PubMed  Google Scholar 

  15. Thamilselvan S, Hackett RL, Khan SR (1997) Lipid peroxidation in ethylene glycol induced hyperoxaluria and calcium oxalate nephrolithiasis. J Urol 157: 1059

    Article  PubMed  Google Scholar 

  16. Thamilselvan S, Byer KJ, Hackett RL, Khan SR (2000) Free radical scavengers, catalase and superoxide dismutase provide protection from oxalate-associated injury to LLC-PK1 and MDCK cells. J Urol 164: 224

    Article  PubMed  Google Scholar 

  17. Blomgren PM, Connors BA, Lingeman JE, Willis LR, Evan AP (1997) Quantitation of shock wave lithotripsy-induced lesions in small and large pig kidneys. Anat Rec 249: 341

    Article  PubMed  Google Scholar 

  18. Lifshitz DA, Lingeman JE, Zafar FS, Hollensbe DW, Nyhuis AW, Evan AP (1998) Alterations in predicted growth rates of pediatric kidneys treated with extracorporeal shockwave lithotripsy. J Endourol 12: 469

    PubMed  Google Scholar 

  19. Streem SB, Yost A, Mascha E (1996) Clinical implications of clinically insignificant store fragments after extracorporeal shock wave lithotripsy. J Urol 155: 1186

    Article  PubMed  Google Scholar 

  20. Delvecchio FC, Preminger GM (2000) Management of residual stones. Urol Clin North Am 27: 347

    Article  PubMed  Google Scholar 

  21. Heimbach D, Kourambas J, Zhong P, Jacobs J, Hesse A, Mueller SC, Delvecchio FC, Cocks FH, Preminger GM (2004) The use of chemical treatments for improved comminution of artificial stones. J Urol 171: 1797

    Article  PubMed  Google Scholar 

  22. Heimbach D, Jacobs D, Hesse A, Muller SC, Zhong P, Preminger GM (1999) How to improve lithotripsy and chemolitholysis of brushite-stones: an in vitro study. Urol Res 27: 266

    Article  PubMed  Google Scholar 

  23. Cicerello E, Merlo F, Gambaro G, Maccatrozzo L, Fandella A, Baggio B, Anselmo G (1994) Effect of alkaline citrate therapy on clearance of residual renal stone fragments after extracorporeal shock wave lithotripsy in sterile calcium and infection nephrolithiasis patients. J Urol 151: 5

    PubMed  Google Scholar 

  24. Strohmaier WL, Pedro M, Wilbert DM, Bichler K-H (1991) Reduction of shock wave-induced tubular alteration by fosfomycin. J. Endourol 5: 57

    Google Scholar 

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Authors and Affiliations

  1. Comprehensive Kidney Stone Center, Division of Urology, Department of Surgery, Duke University Medical Center, 1572D White Zone, DUMC 3167, Durham, NC 27710USA

    Fernando C. Delvecchio, Ricardo M. Brizuela, Zaiquan Li, Pei Zhong & Glenn M. Preminger

  2. Center for the Study of Lithiasis and Pathological Calcification, Division of Experimental Pathology, University of Florida, Gainesville, FL, USA

    Saeed R. Khan & Karen Byer

Authors
  1. Fernando C. Delvecchio
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  2. Ricardo M. Brizuela
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  3. Saeed R. Khan
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  4. Karen Byer
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  5. Zaiquan Li
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  6. Pei Zhong
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  7. Glenn M. Preminger
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Correspondence to Glenn M. Preminger.

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Delvecchio, F.C., Brizuela, R.M., Khan, S.R. et al. Citrate and vitamin E blunt the shock wave-induced free radical surge in an in vitro cell culture model. Urol Res 33, 448–452 (2005). https://doi.org/10.1007/s00240-005-0506-2

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  • DOI: https://doi.org/10.1007/s00240-005-0506-2

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