TY - JOUR
T1 - The renal injury and inflammation caused by ischemia-reperfusion are reduced by genetic inhibition of TNF-αR1
T2 - A comparison with infliximab treatment
AU - Di Paola, Rosanna
AU - Genovese, Tiziana
AU - Impellizzeri, Daniela
AU - Ahmad, Akbar
AU - Cuzzocrea, Salvatore
AU - Esposito, Emanuela
PY - 2013/1/30
Y1 - 2013/1/30
N2 - 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.
AB - 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.
KW - Inflammation
KW - Renal ischemia-reperfusion injury
KW - TNF-αR1 gene deletion
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U2 - 10.1016/j.ejphar.2012.11.066
DO - 10.1016/j.ejphar.2012.11.066
M3 - Article
C2 - 23291313
AN - SCOPUS:84872921643
SN - 0014-2999
VL - 700
SP - 134
EP - 146
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -