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Protective effect of heme oxygenase induction in ischemic acute renal failure
H Shimizu1, T Takahashi, T Suzuki
1Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama City, Japan.
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.
Design:
Randomized, masked, controlled animal study.
Setting:
University-based animal research facility.
Subjects:
Sprague-Dawley male rats, weighing 200-250 g.
Interventions:
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.
Measurements And Main 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.
Conclusion:
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.