Pflügers Archiv

, Volume 446, Issue 1, pp 116–124 | Cite as

The induction of heat shock protein-72 attenuates cisplatin-induced acute renal failure in rats

  • Hua Zhou
  • Akihiko Kato
  • Hideo Yasuda
  • Mari Odamaki
  • Hideaki Itoh
  • Akira Hishida
Renal Function, Body Fluids


Induction of heat shock proteins (HSPs) is thought to play a protective role in ischaemic acute renal failure (ARF). However the role of HSPs in nephrotoxic ARF is not well explored. The aim of this study was to clarify the effects of the induction of HSP70s on cisplatin (CDDP) (6 mg/kg i.v.)-induced ARF in rats. Uranyl acetate (UA) or sodium arsenite (SA) were administered i.v. 14 days or 1 day respectively before CDDP injection to induce HSPs. Serum creatinine (SCr), tubular damage score and the numbers of apoptotic (TUNEL-positive) cells were examined 5 days after CDDP injection. The expression of HSP72, B-cell lymphoma gene product-2 (Bcl-2) and Bax were evaluated by Western blot analysis. We also investigated the effect of co-administration of chelerythrine chloride (Chel), which inhibits the induction of HSPs, with SA on the expression of HSP72 and nephrotoxicity. Pretreatment with UA or SA significantly induced renal HSP72 expression. Both UA and SA attenuated the CDDP-induced increase in SCr and tubular damage scores. Co-administration of Chel with SA abolished the SA-induced increment of HSP72 and the beneficial effects of SA. The protective effects of the induction of HSP72 were associated with an increased renal Bcl-2/Bax ratio and the reduction of TUNEL-positive cells in the outer stripe of outer medulla. Our findings suggest that HSP72 attenuates CDDP-induced nephrotoxicity. The protective effects of HSP72 are associated with an increased Bcl-2/Bax ratio and less apoptosis.


Cisplatin Acute renal failure HSP72 Apoptosis Bcl-2/Bax ratio Sodium arsenite Chelerythrine chloride 



We are grateful to the Nippon Kayaku (Tokyo, Japan) for kindly providing CDDP. Part of this work was presented at the World Congress of Nephrology (San Francisco, October 17-20, 2001). This work was supported by a research grant sponsored by the Ministry of Education, Science, Sports and Culture of Japan.


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Copyright information

© Springer-Verlag  2003

Authors and Affiliations

  • Hua Zhou
    • 1
  • Akihiko Kato
    • 1
  • Hideo Yasuda
    • 1
  • Mari Odamaki
    • 1
  • Hideaki Itoh
    • 2
  • Akira Hishida
    • 1
  1. 1.First Department of MedicineHamamatsu University School of MedicineHamamatsuJapan
  2. 2.Second Department of BiochemistryAkita University School of MedicineAkitaJapan

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