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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

Representative light micrographs of the left liver lobe of sham-operated rats (a) and of the left lobe of rats submitted to ischemia/reperfusion (I/R) (b and c). Hematoxylin and eosin staining. The sham animal shows normal hepatocyte and sinusoid morphology (a). In animals submitted to I/R the lower magnification picture (b) shows decreased eosinophilia of hepatocytes, hepatocyte vacuolation, disarrangement of hepatocyte cords, and altered sinusoidal dilatation (b). An area of extensive hepatocyte necrosis and plate disintegration (black stars) is shown under higher magnification in (c), example of grade 3. P: portal vein; CL: centrolobular vein.
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fig3: Representative light micrographs of the left liver lobe of sham-operated rats (a) and of the left lobe of rats submitted to ischemia/reperfusion (I/R) (b and c). Hematoxylin and eosin staining. The sham animal shows normal hepatocyte and sinusoid morphology (a). In animals submitted to I/R the lower magnification picture (b) shows decreased eosinophilia of hepatocytes, hepatocyte vacuolation, disarrangement of hepatocyte cords, and altered sinusoidal dilatation (b). An area of extensive hepatocyte necrosis and plate disintegration (black stars) is shown under higher magnification in (c), example of grade 3. P: portal vein; CL: centrolobular vein.

Mentions: A semiquantitative evaluation of liver lesions showed a statistically significant difference in the extent of liver damage when comparing sham-operated rats and animals subjected to I/R (Score 0–3: 0.6 ± 0.1 versus 2.4 ± 0.2, resp.). In the ischemic lobe of the animals submitted to I/R several lobules showed a detectable damage. In particular, hepatocyte necrosis and sinusoidal disarrangement (Figures 3(b)-3(c), Grade 3) when compared with sham-operated animals (Figure 3(a)).


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)

Representative light micrographs of the left liver lobe of sham-operated rats (a) and of the left lobe of rats submitted to ischemia/reperfusion (I/R) (b and c). Hematoxylin and eosin staining. The sham animal shows normal hepatocyte and sinusoid morphology (a). In animals submitted to I/R the lower magnification picture (b) shows decreased eosinophilia of hepatocytes, hepatocyte vacuolation, disarrangement of hepatocyte cords, and altered sinusoidal dilatation (b). An area of extensive hepatocyte necrosis and plate disintegration (black stars) is shown under higher magnification in (c), example of grade 3. P: portal vein; CL: centrolobular vein.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Representative light micrographs of the left liver lobe of sham-operated rats (a) and of the left lobe of rats submitted to ischemia/reperfusion (I/R) (b and c). Hematoxylin and eosin staining. The sham animal shows normal hepatocyte and sinusoid morphology (a). In animals submitted to I/R the lower magnification picture (b) shows decreased eosinophilia of hepatocytes, hepatocyte vacuolation, disarrangement of hepatocyte cords, and altered sinusoidal dilatation (b). An area of extensive hepatocyte necrosis and plate disintegration (black stars) is shown under higher magnification in (c), example of grade 3. P: portal vein; CL: centrolobular vein.
Mentions: A semiquantitative evaluation of liver lesions showed a statistically significant difference in the extent of liver damage when comparing sham-operated rats and animals subjected to I/R (Score 0–3: 0.6 ± 0.1 versus 2.4 ± 0.2, resp.). In the ischemic lobe of the animals submitted to I/R several lobules showed a detectable damage. In particular, hepatocyte necrosis and sinusoidal disarrangement (Figures 3(b)-3(c), Grade 3) when compared with sham-operated animals (Figure 3(a)).

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