Heparin, a potent releasing agent of extracellular superoxide dismutase (EC-SOD C), suppresses ischaemic paw oedema in mice.
Heparin (2,000 U/kg, i.v.) increases the plasma superoxide dismutase (SOD) activity by 2-3 times after 5 min. followed by a gradual decrease. A high dose of heparin (4 x 10(3) and 10 x 10(3) U/kg) exhibits a lower increase in the release of SOD. Ischaemic paw oedema in mice was suppressed by various types of SOD and heparin also suppresses this oedema. The dose-dependent curve of heparin of oedema suppression corresponds well with the increased plasma level of SOD. Inducibility with heparin, slow clearance from the bloodstream and blocking of oedema suppression by the copper chelator, diethyldithiocarbamate (DDC), suggest that the oedema suppressing SOD was the extracellular (EC)-SOD C. Other anticoagulants such as citrate and EDTA had no effect. Chondroitin sulphate A and C or carrageenan exhibited weak suppression. A complex of EC-SOD C and heparin appears not to bind to the endothelium in contrast to the injected free EC-SOD C. When heparin is re-injected, more than 1 week was required to get the same degree of oedema suppression. This indicates the necessity of newly synthesized enzyme. A biological role for heparin-induced release of plasma SOD is demonstrated for the first time in this investigation.
Oyanagui
Y
Y
Research Laboratories of Fujisawa Pharmaceutical Co., Osaka, Japan.
Sato
S
S
D000818:Animals; D002351:Carrageenan / Q000494:pharmacology; D002809:Chondroitin Sulfates / Q000494:pharmacology; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D004050:Ditiocarb / Q000494:pharmacology; D004487:Edema / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004492:Edetic Acid / Q000494:pharmacology; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006614:Hindlimb / Q000098:blood supply; D007511:Ischemia / Q000150:complications; D007700:Kinetics; D008297:Male; D051379:Mice; D013482:Superoxide Dismutase / Q000097:blood*
D002951:Citrates; D019343:Citric Acid; D002351:Carrageenan; D006493:Heparin; D002809:Chondroitin Sulfates; D004050:Ditiocarb; D004492:Edetic Acid; D013482:Superoxide Dismutase