Brain and tissue distribution of polyethylene glycol-conjugated superoxide dismutase in rats

Abstract

Background and purpose: 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.

Conclusion: 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.