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

Author:

Yoshida K1,Burton G F1,McKinney J S1,Young H1,Ellis E F1

Affiliation:

1. Department of Pharmacology, Medical College of Virginia, Virginia Commonwealth University, Richmond.

Abstract

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

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Advanced and Specialized Nursing,Cardiology and Cardiovascular Medicine,Neurology (clinical)

Reference30 articles.

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