ABSTRACT
Renal ischemia reperfusion [RIRI] injury is a clinically important problem. The aim of this study was to assess the possible renoprotective effect of inducing heat shock proteins by hydrocortisone and acetylsalicylic acid [ASA] in RIRI in rats. The present study was conducted on 56 male albino rats that were divided into four groups. Group I included normal Sham-operated rats that served as control for group II, Group II was subdivided into Group IIa in which renal ischemia reperfusion injury [RIRI] was induced and group IIb [in which RIRI was induced and received quercetin [HSP70 inhibitor] 24 hours and again 1 hour prior to the induction of RIRI. Groups III and IV consisted of rats with RIRI that received hydrocortisone without [Group IIIa] or with [Group IIIb] quercetin, and that received ASA without [Group IVa] or with [Group IVb] quercetin, respectively, intramuscularly 24 and 12 hours before and after the induction of RIRI. Thirty hours after induction of RIRI, serum urea concentration and creatinine clearance were assessed. Moreover; renal heat shock protein-70 [HSP70] level and renal caspase-3 activity [as an index of apoptosis] were assessed. A significant increase in serum urea concentration and in renal HSP70 level, and caspase-3 activity together with a significant decrease in creatinine clearance, has been observed in non-treated rats [group II] killed 30 hrs after RIRI compared to Sham-operated rats. Administration of hydrocortisone or ASA resulted in a significant decrease in serum urea concentration and in renal caspase-3 activity as well as a significant increase in creatinine clearance and a significant increase in renal HSP70 in rats killed 30 hrs following RIRI [group III and IV] compared to non-treated rats with RIRI. Induction of HSP70 mediated the renoprotective role of both drugs evidenced by a significant decrease in renoprotective effect of either drug in the groups that received quercetin [IIIb and IVb] compared to those that didn't receive quercetin [IIIa and IVa]. This study demonstrates a role for HSP70 in protection against RIRI. Pharmacological strategies to increase stress protein expression have potential merit to prevent ischemic injury to the kidney and other organs. The ability of hydrocortisone and ASA to induce ischemic tolerance suggests that there are advantages in their application in RIRI. First, either is a safe drug in clinical practice. Second, the induction time of ischemic tolerance is relatively rapid after administration of either. Third, there is no additional or special equipment required for the induction of tolerance. Clinical studies will be necessary to evaluate the therapeutic properties of either drug in preventing I/R injury not only in kidneys but also in other solid organs