Pre-treatment with isoflurane ameliorates renal ischemic-reperfusion injury in mice

Aims: Perioperative renal dysfunction is associated with a high mortality. The aim of this study was to investigate whether isoflurane preconditioning provides a protection against renal ischemic-reperfusion injury and whether hypoxia inducible factor 1 alpha (HIF-1 alpha) is responsible for the protection afforded by isoflurane in mice. Main methods: Adult male C57BL/6 mice received vehicle (PBS), scrambled siRNA or HIF-1 alpha siRNA via hydrodynamic injection through tail vein. Twenty-four hours after injection, they were exposed to 1.5% isoflurane in oxygen enriched air for 2 h while controls without injection were exposed to oxygen enriched air. Twenty-four hours after gas exposure, mice were sacrificed and their kidney were harvested for western blot while other cohorts underwent renal ischemia-reperfusion injury induced by bilateral renal pedicle clamping for 25 min for renal histological or functional analysis 24 h after reperfusion or by unilateral clamping for 40 min for survival rate analysis. Key findings: Survival rate and the expression of HIF-1 alpha and erythropoietin were significantly increased while apoptosis, renal tubule score, blood plasma creatinine and urea were decreased by isoflurane preconditioning. HIF-1 alpha siRNA but not scrambled siRNA injection abrogated the protective effect of isoflurane preconditioning. Significance: Our data suggested that isoflurane preconditioning provided a protection against renal ischemic-reperfusion injury which is very likely due to hypoxia inducible factor-1 alpha upregulation. (C) 2011 Elsevier Inc. All rights reserved.