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

Abstract

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 α (HIF-1 α) 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 α siRNA via hydrodynamic injection through tail vein. Twenty-four hours after injection, they were exposed to 1.5% isoflurane in oxygen enriched air for 2h 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 24h after reperfusion or by unilateral clamping for 40 min for survival rate analysis.

KEY FINDINGS:

Survival rate and the expression of HIF-1 α and erythropoietin were significantly increased while apoptosis, renal tubule score, blood plasma creatinine and urea were decreased by isoflurane preconditioning. HIF-1 α 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 α upregulation.

• Authors: Lei Zhang, Han Huang, Jian Cheng, Jin Liu, Hailin Zhao, Marcela P Vizcaychipi, Daqing Ma
• Journal: Life sciences (Life Sci) Vol. 88 Issue 25-26 Pg. 1102-7 (Jun 20 2011) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 21565202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• Protective Agents
• RNA, Small Interfering
• Erythropoietin
• Urea
• Creatinine
• Isoflurane

Topics

• Animals
• Apoptosis (drug effects)
• Blotting, Western
• Creatinine (blood)
• Disease Models, Animal
• Erythropoietin (biosynthesis)
• Hypoxia-Inducible Factor 1, alpha Subunit (biosynthesis, genetics)
• In Situ Nick-End Labeling
• Isoflurane (administration & dosage, pharmacology, therapeutic use)
• Kidney (blood supply, drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Protective Agents (administration & dosage, pharmacology, therapeutic use)
• RNA, Small Interfering (genetics)
• Reperfusion Injury (metabolism, pathology, prevention & control)
• Time Factors
• Urea (blood)