Brain and tissue distribution of polyethylene glycol-conjugated superoxide dismutase in rats.
OBJECTIVE
The purpose of this study was to determine the distribution of polyethylene glycol-conjugated superoxide dismutase in the brain, cerebrospinal fluid, and various organs.


METHODS
Distribution of iodine-125-labeled polyethylene glycol-conjugated superoxide dismutase was determined in three groups of male Sprague-Dawley rats: a normotensive sham control group (n = 9) and groups given 125I-labeled polyethylene glycol-conjugated superoxide dismutase either 30 minutes before (n = 10) or 30 minutes after (n = 7) norepinephrine-induced hypertensive injury.


RESULTS
In the first 30 minutes after intravenous administration, polyethylene glycol-conjugated superoxide dismutase plasma activity declined to 70% of the initial value and then decreased negligibly between 30 and 90 minutes. Levels of 125I-labeled polyethylene glycol-conjugated superoxide dismutase in normotensive animals were low in the brain and cerebrospinal fluid and highest in kidney. Brain levels of polyethylene glycol-conjugated superoxide dismutase were elevated only in those rats that received it before hypertensive injury; however, cerebrospinal fluid levels were elevated in animals receiving the drug either before or after hypertensive injury.


CONCLUSIONS
Our results suggest that the blood-brain barrier becomes more permeable to polyethylene glycol-conjugated superoxide dismutase only during the hypertensive period but that the blood-cerebrospinal fluid barrier sustains more permanent injury. We suggest that the therapeutic effectiveness of polyethylene glycol-conjugated superoxide dismutase in hypertensive brain injury is due to its action in the vascular wall or to its extracellular activity in the cerebrospinal fluid.
Yoshida
K
K
Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Burton
G F
GF
McKinney
J S
JS
Young
H
H
Ellis
E F
EF
D000818:Animals; D001769:Blood / Q000378:metabolism; D001921:Brain / Q000201:enzymology*; D002555:Cerebrospinal Fluid / Q000378:metabolism; D016166:Free Radical Scavengers; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008297:Male; D009638:Norepinephrine; D009994:Osmolar Concentration; D011092:Polyethylene Glycols / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D016166:Free Radical Scavengers; D007457:Iodine Radioisotopes; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D009638:Norepinephrine