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Published in: Intensive Care Medicine 5/2007

01-05-2007 | Experimental

RETRACTED ARTICLE: Glycogen synthase kinase-3β inhibition attenuates the development of ischaemia/reperfusion injury of the gut

Authors: Salvatore Cuzzocrea, Emanuela Mazzon, Emanuela Esposito, Carmelo Muià, Maha Abdelrahman, Rosanna Di Paola, Concetta Crisafulli, Placido Bramanti, Christoph Thiemermann

Published in: Intensive Care Medicine | Issue 5/2007

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Abstract

Objective

This study investigated the effects of TDZD-8, a potent and selective GSK-3β inhibitor, on tissue injury caused by ischaemia/reperfusion (I/R) of the gut.

Design and setting

Animal study in the Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.

Subjects

Splanchnic artery occlusion (SAO) shocked rats.

Interventions

I/R injury of the intestine was caused by clamping both the superior mesenteric artery and the coeliac trunk for 45 min followed by release of the clamp allowing reperfusion for 1 or 6 h. This procedure results in SAO shock.

Measurements and results

Only 10% of the SAO animals survived the entire 6 h reperfusion period. In a separate set of experiments after 60 min of reperfusion animals were killed for histological examination and biochemical studies. Administration of TDZD-8 (1 mg/kg i.v.) 5 min prior to the reperfusion significantly reduced the (a) fall in mean arterial blood pressure, (b) mortality rate, (c) infiltration of the reperfused intestine with polymorphonuclear neutrophils (MPO activity), (d) production of pro-inflammatory cytokines (TNF-α and IL-1β and (e) histological evidence of gut injury. Administration of TDZD-8 also markedly reduced the immunoreactivity of nitrotyrosine formation and the expression of ICAM-1 and P-selectin during reperfusion.

Conclusions

Based on these findings we propose that TDZD-8 would be useful in the treatment of various ischaemia and reperfusion diseases.
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Metadata
Title
RETRACTED ARTICLE: Glycogen synthase kinase-3β inhibition attenuates the development of ischaemia/reperfusion injury of the gut
Authors
Salvatore Cuzzocrea
Emanuela Mazzon
Emanuela Esposito
Carmelo Muià
Maha Abdelrahman
Rosanna Di Paola
Concetta Crisafulli
Placido Bramanti
Christoph Thiemermann
Publication date
01-05-2007
Publisher
Springer Berlin Heidelberg
Published in
Intensive Care Medicine / Issue 5/2007
Print ISSN: 0342-4642
Electronic ISSN: 1432-1238
DOI
https://doi.org/10.1007/s00134-007-0595-1

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