Potential role of cerebral glutathione in the maintenance of blood-brain barrier integrity in rat

Using the model of glutathione (GSH) depletion, possible role of GSH in the maintenance of blood-brain barrier (BBB) integrity was evaluated in rats. Administration (i.p.) of GSH depletors, diethyl maleate (DEM, 1-4 mmol/kg), phorone (2-3 mmol/kg) and 2-cyclohexene-1-one (CHX, 1 mmol/kg), to male ad...

Full description

Saved in:
Bibliographic Details
Published in:Neurochemical research 1999-12, Vol.24 (12), p.1507-1514
Main Authors: AGARWAL, R, SHUKLA, G. S
Format: Article
Language:English
Subjects:
2-Cyclohexene-1-one
Acetaminophen - pharmacology
Acetylcysteine - pharmacology
Animals
Antioxidants - pharmacology
Ascorbic Acid - pharmacology
Biological and medical sciences
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - physiology
Brain - drug effects
Brain - physiology
Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges
Curcuma
diethyl maleate
Fundamental and applied biological sciences. Psychology
Glutathione - antagonists & inhibitors
Glutathione - metabolism
Ketones - pharmacology
Liver - drug effects
Liver - physiology
Male
Maleates - pharmacology
Plant Extracts - pharmacology
Rats
Rats, Inbred Strains
Vertebrates: nervous system and sense organs
Vitamin E - pharmacology
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Using the model of glutathione (GSH) depletion, possible role of GSH in the maintenance of blood-brain barrier (BBB) integrity was evaluated in rats. Administration (i.p.) of GSH depletors, diethyl maleate (DEM, 1-4 mmol/kg), phorone (2-3 mmol/kg) and 2-cyclohexene-1-one (CHX, 1 mmol/kg), to male adults was found to deplete brain and liver GSH and increase the BBB permeability to micromolecular tracers (sodium fluorescein and [14C]sucrose) in a dose-dependent manner at 2h. However, BBB permeability to macromolecular tracers such as horseradish peroxidase and Evan's blue remained unaltered. It was also shown that observed BBB permeability dysfunction was associated with brain GSH depletion. A lower magnitude of BBB increase in rat neonates, as compared to adults, indicated a possible bigger role of GSH in the BBB function of mature brain. The treatment with N-acetylcysteine, methionine and GSH provided a partial to full protection against DEM-induced brain (microvessel) GSH depletion and BBB dysfunction; however, the treatment with alpha-tocopherol, ascorbic acid and turmeric were not effective. Our studies showed that cerebral GSH plays an important role in maintaining the functional BBB integrity.
ISSN:0364-3190
1573-6903
DOI:10.1023/A:1021191729865