Changes in macromolecular permeability by intravascular generation of oxygen-derived free radicals

Klaus Ley, Karl E. Arfors

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

It has been suggested that oxygen derivatives, namely, superoxide anion radical O . 2, hydrogen peroxide H2O2, and hydroxyl radical OH. may play a major role in inflammatory diseases, reperfusion damage after ischemia, and radiation-induced tissue deterioration. Studies of the microcirculation, using the hamster cheek pouch preparation, were carried out in order to assess possible induction of permeability changes by these species. Oxygen-derived free radicals were generated enzymatically in the microvessels by injecting xanthine oxidase via a micropipet. Permeability changes were measured by counting the number of sites at which the systemically circulating fluorescent tracer FITC-dextran (Mw = 150,000) leaked from postcapillary and collecting venules. Additionally, the average light intensity was assessed by means of a photomultiplier. In the cheek pouches which had received a microinjection of xanthine oxidase (0.05 unit/ml) the number of leakage sites reached a maximum of 53.0 ± 32 (mean ± SD) after 40 min, compared to 4.7 in the control group. The photomultiplier readings showed a peak after 50 min, increasing by 30.7 ± 17% (mean ± SD) of the control value before microinjection, while the control group showed no statistically significant change. Intravenous infusion of native superoxide dismutase (SOD) prevented the permeability changes completely. The same effect was obtained with intravenous injection of polyethylene glycol (PEG)-SOD. These results may indicate that administration of PEG-SOD may be an adequate approach for preventing the occurrence of O . 2-induced alterations in microvascular permeability in various diseases.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalMicrovascular Research
Volume24
Issue number1
DOIs
StatePublished - Jul 1982
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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