Preventive Effects of Superoxide Dismutase Derivatives Modified with Monosaccharides on Reperfusion Injury in Rat Liver Transplantation

Background: Superoxide dismutase (SOD) derivatives modified with monosaccharides such as mannosylated SOD (Man-SOD) and galactosylated SOD (Gal-SOD) are taken up by parenchymal and nonparenchymal cells of the liver, respectively, via receptor-mediated endocytosis. We examined the preventive effects of Man- or Gal-SOD on cold ischemia-reperfusion injury in orthotopic liver transplantation (OLT) in rats.

Methods: Male Lewis rats underwent OLT. Native SOD and modified SOD with mannose (Man-SOD) or galactose (Gal-SOD) were intravenously given just prior to reperfusion of the grafted liver.

Results: After OLT, no significant changes in serum levels of aspartate aminotransferase or lactate dehydrogenase were evident among rats, with or without various types of SOD. However, tissue levels of Na+,K+-ATPase, an indicator of tissue viability, were significantly higher in rats treated with Man- and Gal-SODs compared with that in untreated OLT rats. When comparisons were made between Gal-SOD and Man-SOD, higher levels of Na+,K+-ATPase were evident in rats treated with Gal-SOD. Elevations of tissue levels of lipid peroxides were significantly inhibited by modified SODs. The survival rates of rats following OLT after prolonged cold preservation correlated with results of graft viability.

Conclusions: SOD derivatives, particularly Gal-SOD, have protective effects on cold ischemia-reperfusion injury during OLT in rats.