Abstract
Purpose. Warm hepatic ischemia-reperfusion (I/R) injury can lead to multiorgan dysfunction. The aim of the present study was to investigate whether acute liver I/R does affect the function and/or structure of remote organs such as lung, kidney, and heart via modulation of extracellular matrix remodelling. Methods. Male Sprague-Dawley rats were subjected to 30 min partial hepatic ischemia by clamping the hepatic artery and the portal vein. After a 60 min reperfusion, liver, lung, kidney, and heart biopsies and blood samples were collected. Serum hepatic enzymes, creatinine, urea, Troponin I and TNF-alpha, and tissue matrix metalloproteinases (MMP-2, MMP-9), myeloperoxidase (MPO), malondialdehyde (MDA), and morphology were monitored. Results. Serum levels of hepatic enzymes and TNF-alpha were concomitantly increased during hepatic I/R. An increase in hepatic MMP-2 and MMP-9 activities was substantiated by tissue morphology alterations. Notably, acute hepatic I/R affect the lung inasmuch as MMP-9 activity and MPO levels were increased. No difference in MMPs and MPO was observed in kidney and heart. Conclusions. Although the underlying mechanism needs further investigation, this is the first study in which the MMP activation in a distant organ is reported; this event is probably TNF-alpha-mediated and the lung appears as the first remote organ to be involved in hepatic I/R injury.
Highlights
Reperfusion following prolonged ischemia may cause paradoxical damage at several levels
This study shows that moderate acute hepatic ischemia/ reperfusion (I/R) injury increases Matrix metalloproteinases I/R (MMP) activity in the ischemic liver region and in the lung, associated with histological damage in liver, lung, and kidney
A moderate hepatic I/R injury is able to increase MMPs activity in the ischemic region, as previously reported [29, 30], and in the nonischemic lobe associated with several histological signs of interstitial and cellular damage [18]
Summary
Reperfusion following prolonged ischemia may cause paradoxical damage at several levels. Recent data suggested that hepatic I/R injury may cause damage to remote organs such as kidney [4], heart [5], and lung [6]. The Scientific World Journal hepatic I/R injury is associated with lung dysfunction such as neutrophil infiltration, edema, intraalveolar hemorrhage and endothelial activation. Inflammatory cytokines such as TNF-alpha participate to extracellular matrix (ECM) degradation following liver injury, and hepatic TNF-alpha expression has been demonstrated to be parallel with induction of matrix metalloproteinases (MMPs) [9], collagenolytic zinc-dependent enzymes that degrade several ECM constituents such as collagen, gelatin, elastin, and fibronectin [10]. As indicators of remote and local tissue damage and leukocyte infiltration we used malondialdehyde (MDA), an indicator of lipid peroxidation rate, and myeloperoxidase (MPO), a neutrophil marker
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