The induction of heat shock protein-72 attenuates cisplatin-induced acute renal failure in rats.
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.
Zhou
Hua
H
First Department of Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192 Hamamatsu, Shizuoka, Japan.
Kato
Akihiko
A
Yasuda
Hideo
H
Odamaki
Mari
M
Itoh
Hideaki
H
Hishida
Akira
A
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology; D000470:Alkaloids; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000494:pharmacology; D053119:Benzophenanthridines; D015153:Blotting, Western; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009942:Organometallic Compounds / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017670:Sodium Compounds / Q000494:pharmacology; D051028:bcl-2-Associated X Protein
D000470:Alkaloids; D000970:Antineoplastic Agents; D018053:Arsenites; C494828:Bax protein, rat; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D009942:Organometallic Compounds; D010617:Phenanthridines; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017670:Sodium Compounds; D051028:bcl-2-Associated X Protein; C005460:uranyl acetate; C017947:sodium arsenite; D003404:Creatinine; C016299:chelerythrine; D002945:Cisplatin