The renal injury and inflammation caused by ischemia-reperfusion are reduced by genetic inhibition of TNF-αR1: A comparison with infliximab treatment

Rosanna Di Paola, Tiziana Genovese, Daniela Impellizzeri, Akbar Ahmad, Salvatore Cuzzocrea, Emanuela Esposito

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

The role of the tumor necrosis factor (TNF)-α in the pathophysiology of renal ischemia/reperfusion (I/R) injury is unclear. We investigate the effects of TNF-αR1 gene deletion and infliximab administration on the degree of renal injury induced by I/R. TNF-αR1 knockout (TNF-αR1KO) and wild-type (TNF-αWT) mice were subjected to bilateral renal artery occlusion (30 min) and reperfusion (24 h). Infliximab (10 mg/kg subcutaneously, s.c.) was administered 1 h before ischemia. At the end of experiments, urea, creatinine, γGT, and AST were measured to assess renal function and reperfusion injury. Markers of oxidative stress, pro-inflammatory mediators, iNOS, COX-2, and NF-κB signaling pathway were measured. Kidney myeloperoxidase (MPO) activity and malondialdehyde (MDA) levels were measured to study polymorphonuclear cell infiltration and lipid peroxidation. TNF-αR1 gene deletion and infliximab administration prevented the increase of urea, creatinine, γGT, kidney AST levels, iNOS and COX-2 expression, NF-κB translocation, MPO activity and MDA levels. TNF-αR1 gene deletion and infliximab administration lowered the histological evidence of renal damage associated with I/R and caused a reduction of nitrotyrosine suggesting reduced nitrosative stress. Our results demonstrate that TNF-α plays an important role in I/R injury and put forward the hypothesis that modulation of TNF-α expression may represent a novel and possible strategy.

Original languageEnglish (US)
Pages (from-to)134-146
Number of pages13
JournalEuropean Journal of Pharmacology
Volume700
Issue number1-3
DOIs
StatePublished - Jan 30 2013

Keywords

  • Inflammation
  • Renal ischemia-reperfusion injury
  • TNF-αR1 gene deletion

ASJC Scopus subject areas

  • Pharmacology

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