PMID- 11709491
OWN - NLM
STAT- MEDLINE
DCOM- 20020131
LR  - 20121115
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 16
IP  - 1
DP  - 2002 Jan
TI  - Rat liver injury after normothermic ischemia is prevented by a phosphinic matrix 
      metalloproteinase inhibitor.
PG  - 93-5
AB  - Hepatic ischemia occurs in liver transplantation, hemodynamic or cardiogenic 
      shock, and liver resection associated with trauma or tumor. Ischemia/reperfusion 
      (I/R) injury results in microcirculation failure followed by apoptosis and 
      necrosis. Matrix metalloproteinases (MMPs) are involved in many physiological and 
      pathological processes, but their expression and function during liver I/R 
      remains poorly documented. In this study, we evaluated the expression of nine 
      MMPs and their natural inhibitors, tissue inhibitors of MMPs (TIMPs), in a rat 
      model of liver I/R. Analysis of MMP and TIMP expression show that although most 
      of these genes are not constitutively expressed in the normal liver, they are 
      induced in a specific time-dependent manner following I/R. Stromelysin-1, 
      gelatinase B, and collagenase-3 are induced during the early phase of acute liver 
      injury associated with inflammation and increased necrosis/apoptosis, whereas 
      gelatinase A, membrane type-MMP, stromelysin-3, metalloelastase, TIMP-1, and 
      TIMP-2 are essentially detectable during the recovery phase of liver injury 
      corresponding to hepatocyte regeneration. This observation suggested that MMPs 
      and TIMPs could play both deleterious and beneficial roles following I/R. We thus 
      tested the effect of a specific phosphinic MMP inhibitor on acute liver I/R 
      injury. Inhibition of MMP activity was shown to significantly decrease liver 
      injury in ischemic/reperfused liver tissue as assessed by histological studies 
      and serum hepatic enzyme levels. We therefore propose that MMP inhibitors may be 
      of clinical relevance in liver-associated ischemic diseases or after liver 
      transplantation.
FAU - Cursio, Raffaele
AU  - Cursio R
AD  - Laboratoire de Recherches Chirurgicales, IFR50, France.
FAU - Mari, Bernard
AU  - Mari B
FAU - Louis, Krystel
AU  - Louis K
FAU - Rostagno, Philippe
AU  - Rostagno P
FAU - Saint-Paul, Marie-Christine
AU  - Saint-Paul MC
FAU - Giudicelli, Jean
AU  - Giudicelli J
FAU - Bottero, Virginie
AU  - Bottero V
FAU - Anglard, Patrick
AU  - Anglard P
FAU - Yiotakis, Athanasios
AU  - Yiotakis A
FAU - Dive, Vincent
AU  - Dive V
FAU - Gugenheim, Jean
AU  - Gugenheim J
FAU - Auberger, Patrick
AU  - Auberger P
LA  - eng
PT  - Journal Article
DEP - 20011114
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Phosphinic Acids)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Liver/drug effects/enzymology
MH  - Liver Diseases/enzymology/pathology/*prevention & control
MH  - Liver Regeneration
MH  - *Matrix Metalloproteinase Inhibitors
MH  - Matrix Metalloproteinases/genetics/metabolism
MH  - Necrosis
MH  - Phosphinic Acids/pharmacology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Reperfusion Injury/enzymology/pathology/*prevention & control
MH  - Temperature
MH  - Tissue Inhibitor of Metalloproteinases/biosynthesis/genetics
EDAT- 2001/11/16 10:00
MHDA- 2002/02/01 10:01
CRDT- 2001/11/16 10:00
PHST- 2001/11/16 10:00 [pubmed]
PHST- 2002/02/01 10:01 [medline]
PHST- 2001/11/16 10:00 [entrez]
AID - 01-0279fje [pii]
AID - 10.1096/fj.01-0279fje [doi]
PST - ppublish
SO  - FASEB J. 2002 Jan;16(1):93-5. doi: 10.1096/fj.01-0279fje. Epub 2001 Nov 14.