Therapeutic effects of superoxide dismutase derivatives modified with mono- or polysaccharides on hepatic injury induced by ischemia/reperfusion.
Therapeutic effects of four types of recombinant superoxide dismutase (SOD) derivatives, conjugates with polysaccharides, carboxymethyl (SOD-CMD) and diethylaminoethyl (SOD-DEAED) dextrans and galactosylated (Gal-SOD) and mannosylated (Man-SOD) derivatives, on hepatic ischemia/reperfusion injury were studied in rats. Hepatic injury induced by transient occlusion and subsequent reflow of hepatic blood was evaluated by the analysis of biliary excretion of bromosulfophthalein (BSP) injected intravenously. At a dose of 10000 units/kg, native SOD and SOD-DEAE did not show any significant effect and SOD-CMD showed slight effect. On the other hand, Gal-SOD and Man-SOD, targeted to the liver parenchymal and nonparenchymal cells, respectively, by a receptor-mediated endocytosis, exhibited superior inhibitory effects. These results demonstrated that these glycosylated SOD derivatives were useful for the prevention of hepatic ischemia/reperfusion injury.
Fujita
T
T
Department of Basic Pharmaceutics, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Furitsu
H
H
Nishikawa
M
M
Takakura
Y
Y
Sezaki
H
H
Hashida
M
M
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply*; D008297:Male; D009005:Monosaccharides; D011134:Polysaccharides; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000494:pharmacology / Q000627:therapeutic use*
D009005:Monosaccharides; D011134:Polysaccharides; D011994:Recombinant Proteins; D013482:Superoxide Dismutase