Protective effect of heme oxygenase induction in ischemic acute renal failure

Objective: To examine the role of heme oxygenase-1 (H0-1) 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 incision s, and the right kidney was removed. Renal ischemia was performed by left r enal microvascular clamping, followed by reflow of the blood. Measurements and Main Results: Ischemia of the kidney in the uninephrectomi zed rat significantly induced H0-1 messenger RNA, protein, and enzyme activ ity, reaching a maximum at 6 hrs, which was mediated in part through an inc rease in microsomal heme concentration. Heat shock protein 70 was induced e xtremely rapidly, reaching a maximum at 1 hr, suggesting that H0-1 and heat shock protein 70 gene expression are regulated separately. Inhibition of H 0 activity by tin mesoporphyrin, which resulted in an increase in microsoma l heme concentration, significantly exacerbated renal function, as judged b y the sustained increase in serum creatinine concentration and extensive tu bular epithelial cell injuries. In contrast, animals that did not receive t in 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 H0-1 in the isch emic 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 i mportant role in conferring protection on renal cells from oxidative damage caused by heme.