Rapid increase in the activity of enzymes of eicosanoid synthesis in hepatic and extrahepatic tissues after experimental liver transplantation.
Previous studies have demonstrated a marked release of prostanoids from hepatic tissue after liver grafting. In addition, eicosanoid synthesis was shown to be regulated at the level of key enzymes. The present study addressed changes of the local availability of these enzymes during and after porcine orthotopic liver transplantation. We determined kinetic parameters of cyclooxygenase (CO), the initial enzyme of prostaglandin synthesis, of prostacyclin and thromboxane synthase (PCS, TXS), two more peripheral enzymes, in microsomal preparations of hepatic and gluteal muscle biopsies, and the activity of 5-lipoxygenase (5-LO), the key enzyme of leukotriene synthesis. Maximal velocity (Vmax) of CO and PCS showed a 4-fold increase both in liver and gluteal muscle tissue 1 hr after reperfusion of the grafted liver and a more than 20-fold increase after 24 hr (P less than 0.001), whereas apparent affinities (Km) remained unchanged. In contrast, Vmax of TXS and the activity of 5-LO disclosed a striking increase only within the hepatic graft (P less than 0.001). No changes of enzymatic activity could be observed during donor operation, cold storage, and 5 min after reperfusion. Results were independent of the duration of preservation (3 hr and 20 hr with Euro-Collins) and the addition of Iloprost, a prostacyclin-analogue. These results suggest that after liver grafting, abnormalities at the level of local enzyme expression in hepatic and extrahepatic tissues might contribute to preservation damage and systemic injury of the host.
Post
S
S
Department of Surgery, University of Heidelberg, Federal Republic of Germany.
Goerig
M
M
Otto
G
G
Manner
M
M
Foltis
C
C
Hofmann
W
W
Herfarth
C
C
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000032:analysis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000096:biosynthesis*; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000032:analysis; D015289:Leukotrienes / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D016031:Liver Transplantation; D011451:Prostaglandin-Endoperoxide Synthases / Q000032:analysis; D013552:Swine; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000032:analysis
D001095:Arachidonic Acids; D015777:Eicosanoids; D015289:Leukotrienes; D016718:Arachidonic Acid; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003577:Cytochrome P-450 Enzyme System; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase; D015232:Dinoprostone