title: Protective effect of heme oxygenase induction in ischemic acute renal failure.
abstract: OBJECTIVE
  To examine the role of heme oxygenase-1 (HO-1) induction in the recovery of renal function in rats with ischemic acute renal failure.
  
  
  METHODS
  Randomized, masked, controlled animal study.
  
  
  METHODS
  University-based animal research facility.
  
  
  METHODS
  Sprague-Dawley male rats, weighing 200-250 g.
  
  
  METHODS
  Anesthetized rats were subjected to bilateral flank incisions, and the right kidney was removed. Renal ischemia was performed by left renal microvascular clamping, followed by reflow of the blood.
  
  
  RESULTS
  Ischemia of the kidney in the uninephrectomized rat significantly induced HO-1 messenger RNA, protein, and enzyme activity, reaching a maximum at 6 hrs, which was mediated in part through an increase in microsomal heme concentration. Heat shock protein 70 was induced extremely rapidly, reaching a maximum at 1 hr, suggesting that HO-1 and heat shock protein 70 gene expression are regulated separately. Inhibition of HO activity by tin mesoporphyrin, which resulted in an increase in microsomal heme concentration, significantly exacerbated renal function, as judged by the sustained increase in serum creatinine concentration and extensive tubular epithelial cell injuries. In contrast, animals that did not receive tin mesoporphyrin showed normal creatinine concentration and microsomal heme concentration 24 hrs after reperfusion, as well as restoration of abnormal renal histology.
  
  
  CONCLUSIONS
  These findings indicate that the expression of HO-1 in the ischemic kidney may be critical in the recovery of renal cell function in this animal model. These findings also suggest that H0-1 induction may play an important role in conferring protection on renal cells from oxidative damage caused by heme.
authors.affiliation: Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama City, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimizu
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Y
authors.initials: Y
authors.lastname: Odaka
authors.forename: M
authors.initials: M
authors.lastname: Hirakawa
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.forename: R
authors.initials: R
authors.lastname: Akagi
mesh_terms: D000624:5-Aminolevulinate Synthetase; D058186:Acute Kidney Injury / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D004791:Enzyme Inhibitors; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D007511:Ischemia / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008665:Metalloporphyrins; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D008665:Metalloporphyrins; D012333:RNA, Messenger; C055421:tin mesoporphyrin; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase