Abstract
Inhibitory effect of superoxide dismutase derivatives modified with various sugar moieties on hepatic injury was examined in rats. Four types of superoxide dismutase (SOD) derivatives, SOD-carboxymethyl dextran conjugate (SOD-CMD), SOD-diethylaminoethyl dextran conjugate (SOD-DEAED), galactosylated SOD (Gal-SOD), and mannosylated SOD (Man-SOD), were used and hepatic injury induced by ischemia/reperfusion was evaluated by analysis of biliary excretion of bromosulfophthalein (BSP) injected intravenously. SOD and SOD-DEAED did not show significant inhibitory effect. SOD-CMD exhibited a slight recovery of biliary excretion of BSP, but the effect was not significant. On the other hand, Gal-SOD and Man-SOD, which were targeted to the liver parenchymal and non-parenchymal cells respectivery by a receptor-mediated endocytosis, almost completely inhibited the hepatic injury. In particular, Man-SOD showed a great inhibitory effect. These results demonstrated that two types of glycosylated SOD derivatives, Gal-SOD and Man-SOD, were useful for the prevention of hepatic ischemia/reperfusion injury. Thus, targeted derivery of SOD to the liver at a cellular level was achieved by chemical modification with sugars. The findings of the present study also will give useful basic information on the mechanism and prevention of tissue injury induced by ischemia/reperfusion.
