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Lung matrix metalloproteinase activation following partial hepatic ischemia/reperfusion injury in rats.

Palladini G, Ferrigno A, Rizzo V, Tarantola E, Bertone V, Freitas I, Perlini S, Richelmi P, Vairetti M - ScientificWorldJournal (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine and Therapeutics, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Via Ferrata 9A, 27100 Pavia, Italy.

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.

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Related in: MedlinePlus

Bar graphs of MMP-2 and MMP-9 activity in ischemic liver lobe (a), lung (b), heart (c), kidney cortex (d), and medulla (e). Sham-operated group (control, n = 15) has been compared with I/R group (n = 17): *P < 0.05. Data are shown as mean values ± SEM.
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fig2: Bar graphs of MMP-2 and MMP-9 activity in ischemic liver lobe (a), lung (b), heart (c), kidney cortex (d), and medulla (e). Sham-operated group (control, n = 15) has been compared with I/R group (n = 17): *P < 0.05. Data are shown as mean values ± SEM.

Mentions: The activity of gelatinase-A (MMP-2) and gelatinase-B (MMP-9) was evaluated to investigate the extent of hepatic, renal, lung, and heart MMPs activity, potentially inducing interstitial degradation (Figure 2). Both I/R and sham-operated groups showed detectable MMP-2 and MMP-9 activities with the exception of the heart where MMP-9 was not detectable.


Lung matrix metalloproteinase activation following partial hepatic ischemia/reperfusion injury in rats.

Palladini G, Ferrigno A, Rizzo V, Tarantola E, Bertone V, Freitas I, Perlini S, Richelmi P, Vairetti M - ScientificWorldJournal (2014)

Bar graphs of MMP-2 and MMP-9 activity in ischemic liver lobe (a), lung (b), heart (c), kidney cortex (d), and medulla (e). Sham-operated group (control, n = 15) has been compared with I/R group (n = 17): *P < 0.05. Data are shown as mean values ± SEM.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3921999&req=5

fig2: Bar graphs of MMP-2 and MMP-9 activity in ischemic liver lobe (a), lung (b), heart (c), kidney cortex (d), and medulla (e). Sham-operated group (control, n = 15) has been compared with I/R group (n = 17): *P < 0.05. Data are shown as mean values ± SEM.
Mentions: The activity of gelatinase-A (MMP-2) and gelatinase-B (MMP-9) was evaluated to investigate the extent of hepatic, renal, lung, and heart MMPs activity, potentially inducing interstitial degradation (Figure 2). Both I/R and sham-operated groups showed detectable MMP-2 and MMP-9 activities with the exception of the heart where MMP-9 was not detectable.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine and Therapeutics, Fondazione IRCCS Policlinico S. Matteo, University of Pavia, Via Ferrata 9A, 27100 Pavia, Italy.

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.

Show MeSH
Related in: MedlinePlus