Lecithinization of superoxide dismutase potentiates its protective effect against Forssman antiserum-induced elevation in guinea pig airway resistance.
We synthesized lecithinized superoxide dismutase (PC-SOD), in which a lecithin derivative was covalently bound to recombinant human SOD. We selected PC4-SOD (4 molecules of the lecithin derivative bound to each SOD dimer) and PC10-SOD (10 molecules of the derivative to each SOD dimer) for our study. Both of these PC-SOD retained SOD activity in vitro and showed delayed plasma disappearance in vivo in rats. PC-SOD also had 4 to 20 times higher affinity in vitro for several kinds of cells than that of unmodified SOD. Because Forssman antiserum is known to induce bronchial obstruction in guinea pigs via actions of O2-, we studied the effect of PC-SOD on Forssman antiserum-induced respiratory resistance. Unmodified SOD was ineffective at the doses of 1,000 to 30,000 U/kg, whereas PC-SOD showed a dose-dependent inhibitory effect over the range of 10 to 1,000 U/kg. The ED50 of PC4-SOD and PC10-SOD were 140 and 240 U/kg, respectively, at 30 min after the challenge with Forssman antiserum. These findings suggest that the pharmacological potency of PC-SOD is over 200 times more than that of unmodified SOD, and that PC-SOD may have the potential for various clinical applications.
Igarashi
R
R
Division of Drug Delivery Systems, St. Marianna University, Kawasaki, Japan.
Hoshino
J
J
Takenaga
M
M
Kawai
S
S
Morizawa
Y
Y
Yasuda
A
A
Otani
M
M
Mizushima
Y
Y
D000403:Airway Resistance / Q000187:drug effects*; D000818:Animals; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007275:Injections, Intravenous; D007525:Isoelectric Focusing; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D014018:Tissue Distribution
D013482:Superoxide Dismutase