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Investigation of protective effect of hydrogen-rich water against cisplatininduced nephrotoxicity in rats using blood oxygenation level-dependent magnetic resonance imaging

  • Taro Matsushita
  • Yoshinori Kusakabe
  • Akihiro Kitamura
  • Sakie Okada
  • Kenya Murase
Original Article

Abstract

Purpose

The aim of this study was to assess the mechanism of the protective effect of hydrogen-rich water (HW) against cisplatin (CP)-induced nephrotoxicity in rats using blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI).

Materials and methods

Apparent transverse relaxation time-weighted images (T2*WI) were acquired in 28 rats. The control group (n = 7) had free access to standard water (SW) and no CP injection. The CP group (n = 7) had free access to SW and was given a CP injection on day 0. The CP+HW group (n = 7) had free access to HW and had a CP injection. The HW group (n = 7) had free access to HW and no CP injection. The apparent transverse relaxation rate (R2*) was estimated from T2*WI.

Results

In the CP+HW group, the R2* value in the medulla normalized by the value of the day 0 was significantly greater than that in the CP group on days 4 and 7. The creatinine and blood urea nitrogen levels in the CP group were significantly higher than those in the control, CP+HW, and HW groups.

Conclusion

BOLD MRI may be useful for demonstrating the change in R2* in CP-induced nephrotoxicity in rats. The changes in the CP+HW group were suspected to be due to a reduction of cytotoxic oxygen radicals.

Key words

Blood oxygenation level-dependent MRI Cisplatin-induced nephrotoxicity Hydrogen-rich water Oxygen consumption Rats 

References

  1. 1.
    Lieberthal W, Triaca V, Levine J. Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: apoptosis vs. necrosis. Am J Physiol 1996;270:F700–F708.PubMedGoogle Scholar
  2. 2.
    Al-Majed AA, Sayed-Ahmed MM, AI-Yahya AA, Aleisa AM, AI-Rejaje SS, Al-Shabanah OA. Propionyl-L-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model. Pharmacol Res 2006;53:278–286.PubMedCrossRefGoogle Scholar
  3. 3.
    Maliakel DM, Kagiya TV, Nair CK. Prevention of cisplatininduced nephrotoxicity by glucosides of ascorbic acid and alpha-tocopherol. Exp Toxicol Pathol 2008;60:521–527.PubMedCrossRefGoogle Scholar
  4. 4.
    Sayed AA. Proanthocyanidin protects against cisplatininduced nephrotoxicity. Phytother Res 2009;23:1738–1741.PubMedCrossRefGoogle Scholar
  5. 5.
    Ueda N, Kaushal GP, Shah SV. Apoptotic mechanisms in acute renal failure. Am J Med 2000;108:403–415.PubMedCrossRefGoogle Scholar
  6. 6.
    Brady HR, Kone BC, Stromski ME, Zeidel ML, Giebisch G, Gullans SR, et al. Mitochondrial injury: an early event in cisplatin toxicity to renal proximal tubules. Am J Physiol 1990;258:F1181–F1187.PubMedGoogle Scholar
  7. 7.
    Davis CA, Nick HS, Agarwal A. Manganese superoxide dismutase attenuates cisplatin-induced renal injury: importance of superoxide. J Am Soc Nephrol 2001;12:2683–9260.PubMedGoogle Scholar
  8. 8.
    Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 2007;13:688–694.PubMedCrossRefGoogle Scholar
  9. 9.
    Nakashima-Kamimura N, Nishimaki K, Mori T, Asoh S, Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising antitumor activity in mice. Cancer Chemother Pharmacol 2009;64:753–761.PubMedCrossRefGoogle Scholar
  10. 10.
    Kitamura A, Kobayashi S, Matsushita T, Fujinawa H, Murase K. Experimental verification of protective effect of hydrogenrich water against cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced CT. Br J Radiol 2010;83:09–514.CrossRefGoogle Scholar
  11. 11.
    Prasad PV, Epstein FH. Changes in renal medullary pO2 during water diuresis as evaluated by blood oxygenation level-dependent magnetic resonance imaging: effects of aging and cyclooxygenase inhibition. Kidney Int 1999;55:294–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Li LP, Santos EA, Dunkle E, Pierchala L, Prasad P. Effect of nitric oxide synthase inhibition on intrarenal oxygenation as evaluated by blood oxygenation level-dependent magnetic resonance imaging. Invest Radiol 2009;44:67–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Priatna A, Epstein FH, Spokes K, Prasad PV. Evaluation of changes in intrarenal oxygenation in rats using multiple gradient-recalled echo (mGRE) sequence. J Magn Reson Imaging 1999;9:842–846.PubMedCrossRefGoogle Scholar
  14. 14.
    Dos Santos EA, Li LP, Ji L, Prasad PV. Early changes with diabetes in renal medullary hemodynamics as evaluated by fiberoptic probes and BOLD magnetic resonance imaging. Invest Radiol 2007;42:157–162.PubMedCrossRefGoogle Scholar
  15. 15.
    Prasad PV, Edelman RR, Epstein FH. Noninvasive evaluation of intrarenal oxygen with BOLD MRI. Circulation 1996;94:3271–3275.PubMedGoogle Scholar
  16. 16.
    Ries M, Basseau F, Tyndal B, Jones R, Deminiere C, Catargi B, et al. Renal diffusion and BOLD MRI in experimental diabetic nephropathy: blood oxygenation level-dependent. J Magn Reson Imaging 2003;17:104–113.PubMedCrossRefGoogle Scholar
  17. 17.
    Flemming B, Seelinger E, Wronski T, Steer K, Arenz N, Persson PB. Oxygen and renal hemodynamics in the conscious rat. J Am Soc Nephrol 2000;11:18–24.PubMedGoogle Scholar
  18. 18.
    Epstein FH. Oxygen and renal metabolism. Kidney Int 1997;51:381–385.PubMedCrossRefGoogle Scholar
  19. 19.
    Lübbers DW, Baumgärtl H. Heterogeneities and profiles of oxygen pressure in brain and kidney as examples of the pO2 distribution in the living tissue. Kidney Int 1997;51:372–380.PubMedCrossRefGoogle Scholar
  20. 20.
    Jandl JH. Blood: textbook of hematology, 2nd edn. Boston: Little, Brown, 1987; p. 154–157.Google Scholar
  21. 21.
    Nishikawa M, Nagatomi H, Chang BJ, Sato E, Inoue M. Targeting superoxide dismutase to renal proximal tubule cells inhibits mitochondrial injury and renal dysfunction induced by cisplatin. Arch Biochem Biophys 2001;1:78–84.CrossRefGoogle Scholar
  22. 22.
    Calamante F, Lythgoe MF, Gadian DG. Early changes in water diffusion, perfusion, T1, and T2 during focal cerebral ischemia in the rat studied at 8.5 T. Magn Reson Med 1999;41:479–485.PubMedCrossRefGoogle Scholar
  23. 23.
    Yang X, Cao J, Wang X, Li X, Xu Y, Jiang X. Evaluation of renal oxygenation in rat by using R2′ at 3-T magnetic resonance: initial observation. Acad Radiol 2008;15:912–98.PubMedCrossRefGoogle Scholar
  24. 24.
    Brezis M, Agmon Y, Epstein FH. Determinations of intrarenal oxygen. I. Effects of diuretics. Am J Physiol 1994;267:F1059–F1062.PubMedGoogle Scholar
  25. 25.
    Sadowski EA, Djamali A, Wentland AL, Muehrer R, Becker BN, Grist TM, et al. Blood oxygen level-dependent and perfusion magnetic resonance imaging: detecting differences in oxygen bioavailability and blood flow in transplanted kidneys. Magn Reson Imaging 2010;28:56–64.PubMedCrossRefGoogle Scholar
  26. 26.
    Kolgazi M, Arbak S, Alican I. The effect of α-melanocyte stimulating hormone on gentamicin-induced acute nephrotoxicity in rats. J Appl Toxicol 2 2007;27:183–188.CrossRefGoogle Scholar
  27. 27.
    Yousef MI, Saad AA, El-Shennawy LK. Protective effect of grape seed proanthocyanidin extract against oxidative stress induced by cisplatin in rats. Food Chem Toxicol 2009;47:1176–1183.PubMedCrossRefGoogle Scholar
  28. 28.
    Dichey DT, Wu YJ, Muldoon LL, Neuwelt EA. Protection against cisplatin-induced toxicities by N-acetylcysteine and sodium thiosulfate as assessed at the molecular, cellular, and in vivo levels. J Pharmacol Exp Ther 2005;313:1052–1058.CrossRefGoogle Scholar
  29. 29.
    Lieberthal W, Triaca V, Levine J. Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: apoptosis vs. necrosis. Am J Physiol 1996;270:F700–F708.PubMedGoogle Scholar
  30. 30.
    Lee RH, Song JM, Park MY, Kang SK, Kim YK, Jung JS. Cisplatin-induced apoptosis by translocation of endogenous Bax in mouse collecting duct cells. Biochem Pharmacol 2001;62:1013–1023.PubMedCrossRefGoogle Scholar
  31. 31.
    Baek SM, Kwon CH, Kim JH, Woo JS, Jung JS, Kim YK. Differential roles of hydrogen peroxide and hydroxyl radical in cisplatin-induced cell death in renal proximal tubular epithelial cells. J Lab Clin Med 2003;142:178–186.PubMedCrossRefGoogle Scholar
  32. 32.
    Zhou H, Miyaji T, Kato A, Fujigaki Y, Sano K, Hishida A. Attenuation of cisplatin-induced acute renal failure is associated with less apoptotic cell death. J Lab Clin Med 1999;134:649–658.PubMedCrossRefGoogle Scholar
  33. 33.
    Pedersen M, Vajda Z, Stodkilde-Jorgensen H, Nielsen S, Frokiaer J. Furosemide increases water content in renal tissue. Am J Physiol Renal Physiol 2007;292:F1645–F1651.PubMedCrossRefGoogle Scholar
  34. 34.
    Malvezzi P, Bricault I, Terrier N, Bayle F. Evaluation of intrarenal oxygenation by blood oxygen level-dependent magnetic resonance imaging in living kidney donors and their recipients: preliminary results. Transpl Proc 2009;41:641–644.CrossRefGoogle Scholar
  35. 35.
    Han F, Xiao W, Xu Y, Wu J, Wang Q, Wang H, et al. The significance of BOLD MRI in differentiation between renal transplant rejection and acute tubular necrosis. Nephrol Dial Transplant 2008;23:2666–2672.PubMedCrossRefGoogle Scholar

Copyright information

© Japan Radiological Society 2011

Authors and Affiliations

  • Taro Matsushita
    • 1
  • Yoshinori Kusakabe
    • 1
  • Akihiro Kitamura
    • 1
  • Sakie Okada
    • 1
  • Kenya Murase
    • 1
  1. 1.Department of Medical Physics and Engineering, Division of Medical Technology and Science, Faculty of Health Science, Graduate School of MedicineOsaka UniversitySuita, OsakaJapan

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