Protective effect of heme oxygenase induction in ischemic acute renal failure.
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.
Shimizu
H
H
Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama City, Japan.
Takahashi
T
T
Suzuki
T
T
Yamasaki
A
A
Fujiwara
T
T
Odaka
Y
Y
Hirakawa
M
M
Fujita
H
H
Akagi
R
R
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
D004791:Enzyme Inhibitors; D018840:HSP70 Heat-Shock Proteins; D008665:Metalloporphyrins; D012333:RNA, Messenger; C055421:tin mesoporphyrin; D006419:Heme Oxygenase (Decyclizing); D000624:5-Aminolevulinate Synthetase