Limits...
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.

Show MeSH

Related in: MedlinePlus

Representative light micrographs of kidney samples obtained from sham-operated rats (a, b, and c) and from rats submitted to hepatic ischemia/reperfusion (I/R) (d, e, and f). Cortex (a, b), outer medulla (c, d), and inner medulla (e; f) are illustrated. Hematoxylin and eosin staining. With respect to the normal morphology of the cortex of sham animals (a), the cortex of animals submitted to hepatic I/R (b) shows dilated interstitium and injury to a few tubules. The insets in (a) show a normal distal convolute tubule (DCT) and in (b) patchy areas of dilatation. With respect to the normal morphology of the outer medulla of sham animals (c), the outer medulla of animals submitted to hepatic I/R shows extended areas of interstitial fluid (asterisk) apparently displacing thick limbs of Henle's loop (THL). Respect to the inner medulla of sham animals (e), the inner medulla of animals submitted to I/R (f), shows slightly dilated thin limbs of Henle's loop (tHL) and increased cellularity in the stromal.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3921999&req=5

fig4: Representative light micrographs of kidney samples obtained from sham-operated rats (a, b, and c) and from rats submitted to hepatic ischemia/reperfusion (I/R) (d, e, and f). Cortex (a, b), outer medulla (c, d), and inner medulla (e; f) are illustrated. Hematoxylin and eosin staining. With respect to the normal morphology of the cortex of sham animals (a), the cortex of animals submitted to hepatic I/R (b) shows dilated interstitium and injury to a few tubules. The insets in (a) show a normal distal convolute tubule (DCT) and in (b) patchy areas of dilatation. With respect to the normal morphology of the outer medulla of sham animals (c), the outer medulla of animals submitted to hepatic I/R shows extended areas of interstitial fluid (asterisk) apparently displacing thick limbs of Henle's loop (THL). Respect to the inner medulla of sham animals (e), the inner medulla of animals submitted to I/R (f), shows slightly dilated thin limbs of Henle's loop (tHL) and increased cellularity in the stromal.

Mentions: When compared with the cortex of sham-operated animals (Figure 4(a) and inset), the cortex of animals submitted to hepatic I/R showed dilated interstitium. Rats submitted to I/R showed damage to tubules with loss of brush border and presence of cellular debris (Figure 4(b) and inset). No significant damage to glomeruli was detected. With respect to the outer medulla of sham animals (Figure 4(c)), the outer medulla of rats submitted to hepatic I/R showed wider areas of interstitial fluid accumulation in the interstitium and disarrangement of thick limbs of Henle's loop (Figure 4(d)). In the inner medulla of animals submitted to I/R, a few thin limbs of Henle's loop appear dilated and with increased cellularity in the stromal (Figure 4(f)) with respect to sham animals (Figure 4(e)).


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 kidney samples obtained from sham-operated rats (a, b, and c) and from rats submitted to hepatic ischemia/reperfusion (I/R) (d, e, and f). Cortex (a, b), outer medulla (c, d), and inner medulla (e; f) are illustrated. Hematoxylin and eosin staining. With respect to the normal morphology of the cortex of sham animals (a), the cortex of animals submitted to hepatic I/R (b) shows dilated interstitium and injury to a few tubules. The insets in (a) show a normal distal convolute tubule (DCT) and in (b) patchy areas of dilatation. With respect to the normal morphology of the outer medulla of sham animals (c), the outer medulla of animals submitted to hepatic I/R shows extended areas of interstitial fluid (asterisk) apparently displacing thick limbs of Henle's loop (THL). Respect to the inner medulla of sham animals (e), the inner medulla of animals submitted to I/R (f), shows slightly dilated thin limbs of Henle's loop (tHL) and increased cellularity in the stromal.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Representative light micrographs of kidney samples obtained from sham-operated rats (a, b, and c) and from rats submitted to hepatic ischemia/reperfusion (I/R) (d, e, and f). Cortex (a, b), outer medulla (c, d), and inner medulla (e; f) are illustrated. Hematoxylin and eosin staining. With respect to the normal morphology of the cortex of sham animals (a), the cortex of animals submitted to hepatic I/R (b) shows dilated interstitium and injury to a few tubules. The insets in (a) show a normal distal convolute tubule (DCT) and in (b) patchy areas of dilatation. With respect to the normal morphology of the outer medulla of sham animals (c), the outer medulla of animals submitted to hepatic I/R shows extended areas of interstitial fluid (asterisk) apparently displacing thick limbs of Henle's loop (THL). Respect to the inner medulla of sham animals (e), the inner medulla of animals submitted to I/R (f), shows slightly dilated thin limbs of Henle's loop (tHL) and increased cellularity in the stromal.
Mentions: When compared with the cortex of sham-operated animals (Figure 4(a) and inset), the cortex of animals submitted to hepatic I/R showed dilated interstitium. Rats submitted to I/R showed damage to tubules with loss of brush border and presence of cellular debris (Figure 4(b) and inset). No significant damage to glomeruli was detected. With respect to the outer medulla of sham animals (Figure 4(c)), the outer medulla of rats submitted to hepatic I/R showed wider areas of interstitial fluid accumulation in the interstitium and disarrangement of thick limbs of Henle's loop (Figure 4(d)). In the inner medulla of animals submitted to I/R, a few thin limbs of Henle's loop appear dilated and with increased cellularity in the stromal (Figure 4(f)) with respect to sham animals (Figure 4(e)).

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