Chronic treatment with rofecoxib but not ischemic preconditioning of the myocardium ameliorates early intestinal damage following cardiac ischemia/reperfusion injury in rats

There is some recent evidence that cardiac ischemia/reperfusion (I/R) injury induces intestinal damage within days, which contributes to adverse cardiovascular outcomes after myocardial infarction. However, it is not clear whether remote gut injury has any detectable early signs, and whether differe...

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Main Authors: László Szilvia Bianka
Lázár Bernadette
Brenner Gábor
Makkos András
Balogh Mihály
Al-Khrasani Mahmoud
Hutka Barbara
Mohammadzadeh Amir
Kemény Ágnes
Horváthné László Terézia
Scheich Bálint
Szabados Tamara
Kenyeres Éva
Giricz Zoltán
Bencsik Péter
Varga Zoltán
Novák Julianna
Helyes Zsuzsanna
Ferdinandy Péter
Gyires Klára
Zádori Zoltán Sándor
Format: Article
Published: 2020
Series:BIOCHEMICAL PHARMACOLOGY 178
Subjects:
doi:10.1016/j.bcp.2020.114099

mtmt:31348421
Online Access:http://publicatio.bibl.u-szeged.hu/22556
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Summary:There is some recent evidence that cardiac ischemia/reperfusion (I/R) injury induces intestinal damage within days, which contributes to adverse cardiovascular outcomes after myocardial infarction. However, it is not clear whether remote gut injury has any detectable early signs, and whether different interventions aiming to reduce cardiac damage are also effective at protecting the intestine. Previously, we found that chronic treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2 (COX-2), limited myocardial infarct size to a comparable extent as cardiac ischemic preconditioning (IPC) in rats subjected to 30-min coronary artery occlusion and 120-min reperfusion. In the present study, we aimed to analyse the early intestinal alterations caused by cardiac I/R injury, with or without the above-mentioned infart size-limiting interventions. We found that cardiac I/R injury induced histological changes in the small intestine within 2 hours, which were accompanied by elevated tissue level of COX-2 and showed positive correlation with the activity of matrix metalloproteinase-2 (MMP-2), but not of MMP-9 in the plasma. All these changes were prevented by rofecoxib treatment. By contrast, cardiac IPC failed to reduce intestinal injury and plasma MMP-2 activity, although it prevented the transient reduction in jejunal blood flow in response to cardiac I/R. Our results demonstrate for the first time that rapid development of intestinal damage follows cardiac I/R, and that two similarly effective infarct size-limiting interventions, rofecoxib treatment and cardiac IPC, have different impacts on cardiac I/R-induced gut injury. Furthermore, intestinal damage correlates with plasma MMP-2 activity, which may be a biomarker for its early diagnosis.
Physical Description:Terjedelem: 14-Azonosító: 114099
ISSN:0006-2952