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Matrix Metalloproteinase Inhibition Protects Rat Livers from Prolonged Cold Ischemia-warm Reperfusion Injury by Virginie Defamie; Marina Laurens; Damiano Patrono; Laurent Devel; Antoine Brault; Marie-Christine Saint-Paul; Athanasios Yiotakis; Pascal Barbry; Jean Gugenheim; Dominique Crenesse; Vincent Dive; Pierre-Michel Huet; Bernard Mari is a Medicine article available to read on EtoBox.

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Matrix metalloproteinases (MMPs) have been implicated in the hepatic injury induced after cold ischemia-warm reperfusion (CI-WR), by altering the extracellular matrix (ECM), but their precise role remains unknown. The hepatic MMP expression was evaluated after 2 conditions of CI (4 degrees C for 24 and 42 hours: viable and nonviable livers) followed by different periods of WR, using isolated perfused rat livers. CI-WR induced moderate changes in hepatic MMP transcript levels not influenced by CI duration, whereas gelatinase activities accumulated in liver effluents. Therefore, the protective effect of a new phosphinic MMP inhibitor, RXP409, was tested after prolonged CI. RXP409 (10 microM) was added to the University of Wisconsin solution, and livers were preserved for 42 hours (4 degrees C), then reperfused for 1 hour in Krebs solution (37 degrees C), containing 20% erythrocytes. Liver viability parameters were recorded, and the extent of cell necrosis was evaluated on liver biopsies, using trypan blue nuclear uptake. Treatment with RXP409 significantly improved liver function (transaminase release and bile secretion) and liver injury. In particular, the MMP inhibitor significantl

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Author

Virginie Defamie; Marina Laurens; Damiano Patrono; Laurent Devel; Antoine Brault; Marie-Christine Saint-Paul; Athanasios Yiotakis; Pascal Barbry; Jean Gugenheim; Dominique Crenesse; Vincent Dive; Pierre-Michel Huet; Bernard Mari

Publisher

Ovid Technologies (Wolters Kluwer Health)

Published

2007

Language

EN

Field

Medicine (Health Sciences)