Prevention of reperfusion liver injury by SOD-(DIVEMA) conjugate

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Procedures for prolongation of superoxide dismutase (SOD) activity both in vitro and in vivo were established by synthesizing the conjugates with the copolymer of the divinyl ether and maleic anhydride (DIVEMA), which have average molecular weigh of 30,000 and 5,000 and narrow molecular weigh distribution (Wm/Mn=1.4). The enzymatic activity of SOD decreased to 50% within 139 min.in human plasma, on the contrary SOD-DIVEMA showed no decrease in 24 hr. SOD injected into mice lost 50% of its activity within 6 min., whereas a half life of SOD in conjugate was 69 min. The conjugating of DIVEMA markedly diminished antigenicity of SOD and increased the stability for temperature. While, an intravital fluorescence epi-illuminated television microscopic observation and analyzing system was newly developed by this Grant in order to estimate the efficacy of conjugating with DIVEMA on the prevention of reperfusion injury of the liver microcirculation. Sodium fluorescein and Rodamin-6G were used for staining serum and leukocyte. The liver microcirculation was recorded under our newly developed epi-illumination video microscope for 30min.after decramping the portal vein. Cramping of the portal vein was continued for 30 min.and a tested drug was administered one min.prior to decramping. The perfusion rate (No.of perfusing sinusoid per acine/Total number of sinusoid), the number of sticking and rolling leukocytes in the lobulus, and the rate of sticking and rolling leukocytes (No.of sticking and rolling leukocytes/total No.of passsing leukocyte) in the post sinusoidal central venule were used as indicators for the reperfusion injury of the liver. Administration of SOD-DIVEMA conjugate prevented reperfusion injury significantly (p<0.05) in compare to SOD administration. On the other hand SOD showed insignificantly better microcirculation estimated in every applied indicators than non treated control.