Prevention of hepatic ischemia-reperfusion injury by SOD-DIVEMA conjugate.
A protective effect of the SOD (superoxide dismutase)-DIVEMA (divinyl ether and maleic anhydride) conjugate on I-R (ischemia-reperfusion) liver injury was demonstrated. Twenty minutes of normothermic hepatic ischemia was induced by clamping the portal triad of Sprague-Dawley rats. Five minutes before the end of ischemia, SOD, SOD-DIVEMA, or NaCl (0.9%) was given intravenously. Using intravital fluorescence microscopy, hepatic microvascular perfusion was analyzed before ischemia and repeatedly during the 120-min reperfusion period. SOD-DIVEMA significantly restored the sinusoidal perfusion rate (control, 98.0 +/- 0.5; NaCl, 65.5 +/- 7. 7; SOD, 81.5 +/- 8.2; SOD-DIVEMA, 95.8 +/- 0.7%) and reduced the number of leukocytes stagnant in acini (control, 4.4 +/- 0.9; NaCl, 36.6 +/- 6.3; SOD, 27.7 +/- 6.8; SOD-DIVEMA, 12.3 +/- 3.3 cells/lobule) and adherent in postsinusoidal venules (control, 55.0 +/- 24; NaCl, 417 +/- 63; SOD, 253 +/- 58; SOD-DIVEMA, 40.0 +/- 14 cells/mm2). In addition, SOD-DIVEMA maintained postischemic hepatocellular integrity. The SOD-DIVEMA-treated group revealed higher serum SOD enzyme activity compared to the SOD group after 120 min of reperfusion (SOD-DIVEMA, 33.0 +/- 5.9; SOD, 8.6 +/- 3.1 U/ml). The beneficial effect of SOD-DIVEMA was most prominent after 120 min of reperfusion, indicating a longer intravascular half-life of SOD-DIVEMA.
Kondo
T
T
Institute for Surgical Research, Klinikum Grosshadern, University of Munich, Munich, D-81377, Germany.
Terajima
H
H
Todoroki
T
T
Hirano
T
T
Ito
Y
Y
Usia
T
T
Messmer
K
K
D000818:Animals; D004338:Drug Combinations; D007511:Ischemia / Q000517:prevention & control*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D011713:Pyran Copolymer / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000097:blood / Q000627:therapeutic use*
D004338:Drug Combinations; D011713:Pyran Copolymer; D013482:Superoxide Dismutase