Effect of Superoxide Dismutase Derivatives Modified with Monosaccharides on Reperfusion Injury of Orthotopic Liver Transplantation in Rats -Evaluation by Liver Na⁺, K⁺-ATpase Activity-

Akihiko Mizoe, Satoshi Kondo, Yukiaki Watanabe, Takashi Azuma, Hikaru Fujioka, Kimiro Tanaka, Koichi Motojima, Kunihide Izawa*, Takashi Kanematsu

Second Department of Surgery and *Department of Emergency, Nagasaki University School of Medicine

Reactive oxygen and oxygen radical scavenger superoxide dismutase (SOD) derivatives were examined in rat orthotopic liver transplantation. We used SOD derivatives modified with monosaccharides such as mannosylated SOD and galactosylated SOD which are rapidly eliminated from the blood circulation and taken up by parenchymal and nonparenchymal cells of the liver, respectively, after intravenous administration. And we determined the effect on reperfusion injury of liver grafts with or without these SOD derivatives. Orthotopic liver transplantation in Lewis male rats was performed under ethyl ether anesthesia. During the operation, native SOD and SOD derivatives were administered by intravenous injection before reperfusion of the graft. Animals were sacrificed 30 minutes after reperfusion, and then their blood samples and liver tissues were procured and analyzed for tissue Na⁺, K⁺-ATPase activities, lipid peroxides (LPO) and SOD activities, and serum biochemical tests were performed. After reperfusion, the levels of serum GOT and LDH were markedly increased and tissue Na⁺, K⁺-ATPase activities were decreased significantly, compared to those in the control rat livers. Tissue LPO were elevated and tissue SOD activities were decreased after reperfusion. The use of SOD derivatives, particularly galactosylated SOD, before reperfusion prevented the depression of tissue Na⁺, K⁺-ATPase activities and improved the levels of tissue LPO and SOD activities. In conclusion, reperfusion of the liver graft led to the production of oxygen free radicals and reperfusion injury was not prevented bv native SOD, but SOD derivatives, particularly galactosylated SOD, had a significant effect on reperfusion injury of the liver graft.

Key words
orthotopic liver transplantation, reperfusion injury, Na⁺, K⁺-ATPase activity, SOD derivatives modified with monosaccharides

Reprint requests
Akihiko Mizoe Second Department of Surgery, Nagasaki University School of Medicine
1-7-1 Sakamoto, Nagasaki, 852 JAPAN

Accepted
March 8, 1995

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