Suppression of carrageenan paw oedema in rats and mice by heparin-induced EC-SODs.
Carrageenan-induced paw edemata of mice and rats were suppressed by 1-4 x 10(3) U/kg intravenous injection of heparin. High doses were less suppressive, corresponding well to the increase in plasma SOD activity. This biphasic dose response curve was also observed in our ischemic paw model of mice. Increased SOD appeared as high molecular EC-SOD C (in mice) and B (in rats) as a result of its sensitivity to a copper chelator and long retention time in the blood stream, compared to the short life of cytosolic Cu, Zn-SOD. EC-SOD C (135 kDa) failed to be detected in the plasma of heparin-injected mice by way of nitroblue tetrazolium staining after PAGE electrophoresis. Instead, SOD activity was found near 270 kDa. An excess heparin-loaded subunit of this enzyme might become inactivated or might not be able to fix to a pocket where EC-SOD eliminates O2-, to protect the endothelium, Electrophoresis dissociates the excess heparin resulting in an active form of the enzyme. Paw edemata of rats were less sensitive because this species lacks the strongly heparin-binding EC-SOD C and has only the weakly heparin-binding EC-SOD B, Ischemia-induced mitochondrial swelling of the paw muscle was observed by electron microscopy and was prevented by heparin injection.
Oyanagui
Y
Y
Drug Development Laboratories of Fujisawa Pharmaceutical Co., Osaka, Japan.
Sato
S
S
D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D004790:Enzyme Induction / Q000187:drug effects; D005110:Extracellular Space / Q000201:enzymology; D005528:Foot / Q000098:blood supply; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007511:Ischemia / Q000150:complications; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000502:physiology*
D002351:Carrageenan; D006493:Heparin; D013482:Superoxide Dismutase