Pretreatment with the tumor nerosis factor-alpha blocker etanercept attenuated ischemia-reperfusion renal injury.

Abstract:

INTRODUCTION:Tumor necrosis factor (TNF)-alpha mediates inflammation and apoptosis in ischemia-reperfusion (IR) injury of the kidneys. Etanercept, a soluble TNF-alpha receptor, has shown anti-inflammatory and anti-apoptotic effects in several animal models of renal injury, including chronic insufficiency and unilateral ureteral obstruction. We evaluated the protective effect of etanercept against experimental renal IR injury. METHODS:Male Sprague-Dawley (SD) rats were divided into 4 groups: saline-treated sham rats, etanercept-treated sham rats, saline-treated IR rats, and etanercept-treated IR rats. Renal messenger RNA (mRNA) levels of TNF-alpha and monocyte chemotactic protein-1 (MCP-1) were measured by real-time polymerase chain reaction (PCR) at 24 hours after IR injury. The protein levels of renal Bcl-2 associated X (Bax), B-cell lymphoma 2 (Bcl), extracellular signal-regulated kinase (ERK), and caspase-3 activation were evaluated using Western blot analysis. The degree of apoptosis of renal tubular cells was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. RESULTS:At 24 hours after IR injury, the serum levels of blood urea nitrogen (BUN) and creatinine were significantly lower among etanercept-treated than saline-treated IR rats. Renal mRNA levels of TNF-alpha and MCP-1 in saline-treated IR rats were significantly higher than the levels in saline-treated sham rats, and TNF-alpha and MCP-1 mRNA levels in etanercept-treated IR rats were significantly lower than those in saline-treated IR rats. Etanercept pretreatment of IR-injured rats significantly increased EKR phosphorylation and reduced the renal Bcl-2/Bax ratio, the renal caspase-3 activation, and the number of TUNEL-positive apoptotic cells. CONCLUSION:Etanercept improved resistance to renal injury during IR by enhancing the activation of ERK and increasing the Bcl-2/Bax ratio.

journal_name

Transplant Proc

authors

Choi DE,Jeong JY,Lim BJ,Na KR,Shin YT,Lee KW

doi

10.1016/j.transproceed.2009.05.042

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

3590-6

issue

9

eissn

0041-1345

issn

1873-2623

pii

S0041-1345(09)01442-0

journal_volume

41

pub_type

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