Pharmacokinetics of extracellular-superoxide dismutase in the vascular system

Free Radic Biol Med. 1993 Feb;14(2):185-90. doi: 10.1016/0891-5849(93)90009-j.


Extracellular-superoxide dismutase C (EC-SOD C) is a secretory tetrameric Cu- and Zn-containing glycoprotein which has high affinity for heparin and heparan sulfate. Upon intravenous injection into rabbits, recombinant human (rh) EC-SOD C was found to be rapidly 97-98% sequestered to the vascular wall, forming an equilibrium with the plasma phase. Recombinant EC-SOD truncation variants with reduced, T216, and without, T213, heparin affinity were found to be sequestered to a reduced extent and not at all, respectively, establishing the importance of the heparin affinity for this behaviour. The halflife of rhEC-SOD C in the vasculature was of the order of 20 h. Injection of large doses resulted in saturation of the binding of rhEC-SOD C to the vascular wall. Scatchard analysis revealed a heterogeneity in affinity of the ligands on the vascular wall. The maximal binding capacity was very high. The equilibration of rhEC-SOD C to the vascular wall of an organ, clamped during enzyme injection, and the primary equilibration phase was studied by comparing binding to a clamped and reperfused kidney with binding to the contralateral control kidney. rhEC-SOD C injected in a low dose was found to equilibrate very slowly to the reperfused kidney with a halftime of about 2 h. With higher rhEC-SOD C doses, at which evidence for saturation is seen, and with the variant rhEC-SOD with reduced heparin affinity. T216, very rapid equilibrations were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / metabolism*
  • Female
  • Free Radicals
  • Genetic Variation
  • Heparin / metabolism
  • Ischemia
  • Kidney / blood supply
  • Kinetics
  • Male
  • Rabbits
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacokinetics
  • Reperfusion
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase / pharmacokinetics*
  • Superoxides / metabolism


  • Free Radicals
  • Recombinant Proteins
  • Superoxides
  • Heparin
  • Superoxide Dismutase