Glutamine treatment attenuates the development of ischaemia/reperfusion injury of the gut.
Intestinal ischemia/reperfusion causes tissue hypoxia and damage, leading to the pathophysiology of inflammation. The aim of this study was to investigate the effects of glutamine on the tissue injury caused by ischemia/reperfusion of the gut. Ischemia/reperfusion injury of the intestine was caused by clamping both the superior mesenteric artery and the celiac trunk for 30 min followed by the release of the clamp allowing reperfusion for 1h. This procedure results in splanchnic artery occlusion-injury. Based on our findings we propose that the amino acid glutamine, administered 15 min before reperfusion at the dose of 1.5mg/kg, i.v. may be useful in the treatment of various ischemia and reperfusion diseases. The present study was performed in order to determine the pharmacological effects of glutamine ischemia/reperfusion-induced intestinal injury in rats. In particular, to gain a better insight into the mechanism(s) of action of glutamine, we evaluated the following endpoints of the inflammatory response: (1) histological damage; (2) neutrophil infiltration of the reperfused intestine (MPO activity); (3) NF-kappaB activation and cytokines production; (4) expression of ICAM-1 and P-selectin during reperfusion; (5) nitrotyrosine and poly-ADP-ribose formation; (6) pro-inflammatory cytokine production; (7) inducible nitric oxide synthase expression; (8) apoptosis as shown by TUNEL staining and (9) Bax/Bcl-2 expression.
Mondello
Stefania
S
Department of Internal Medicine, University of Messina, Italy.
Galuppo
Maria
M
Mazzon
Emanuela
E
Domenico
Italiano
I
Mondello
Patrizia
P
Carmela
Aloisi
A
Cuzzocrea
Salvatore
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005973:Glutamine / Q000627:therapeutic use*; D051550:I-kappa B Kinase / Q000378:metabolism; D007077:Ileal Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007082:Ileum / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D021381:Protein Transport; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013152:Splanchnic Circulation / Q000187:drug effects; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D005973:Glutamine; D011064:Poly Adenosine Diphosphate Ribose; C002744:3-nitrotyrosine; D014443:Tyrosine; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051550:I-kappa B Kinase