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

Autor: Zsuzsanna Helyes, Mihaly Balogh, Klára Gyires, Szilvia B. László, Bernadette Lázár, Péter Ferdinandy, Tamara Szabados, Péter Bencsik, Ágnes Kemény, András Makkos, Amir Mohammadzadeh, Éva Kenyeres, Terézia László, Zoltán S. Zádori, Mahmoud Al-Khrasani, Zoltán Varga, Julianna Novák, Barbara Hutka, Gábor B. Brenner, Zoltán Giricz, Bálint Scheich
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Cardiotonic Agents
Gene Expression
Myocardial Reperfusion Injury
Matrix metalloproteinase
Biochemistry
Drug Administration Schedule
03 medical and health sciences
Lactones
0302 clinical medicine
Internal medicine
Intestine
Small
medicine
Animals
Myocardial infarction
Sulfones
Rats
Wistar
Ischemic Preconditioning
Rofecoxib
Pharmacology
Cyclooxygenase 2 Inhibitors
business.industry
Myocardium
Blood flow
medicine.disease
Coronary Vessels
Small intestine
3. Good health
Rats
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Coronary Occlusion
Matrix Metalloproteinase 9
Cyclooxygenase 2
030220 oncology & carcinogenesis
Cardiology
Ischemic preconditioning
Biomarker (medicine)
Matrix Metalloproteinase 2
business
Reperfusion injury
Biomarkers
medicine.drug
Zdroj: Biochemical Pharmacology
ISSN: 0006-2952
DOI: 10.1016/j.bcp.2020.114099
Popis: 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 h, 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.
Databáze: OpenAIRE
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