Document Detail

Inhibition of iron-dependent and ischemia-induced brain damage by the alpha-tocopherol analogue MDL 74,722.
MedLine Citation:
PMID:  9918709     Owner:  NLM     Status:  MEDLINE    
Free radical-induced lipid peroxidation is an important factor in the pathogenesis of ischemic brain damage. We studied the effects of the alpha-tocopherol analogue MDL 74,722 on iron-dependent lipid peroxidation and infarct volume after transient focal cerebral ischemia. The effects of MDL 74,722 on iron-induced lipid peroxidation were tested in cerebellar granule cell cultures by means of a thiobarbituric acid reactive substances (TBARS) assay. The absorbance resulting from mitochondrial reduction of 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) was taken as a measure of cell viability. Besides, in male Wistar rats the left middle cerebral artery (MCA) was occluded for 3 h by means of an intraluminal filament. Rats were treated with vehicle (n = 19) or MDL 74,722 (n = 17), administered intravenously for 3 h in a dose of 2 mg/(kg.h), starting 105 min after MCA occlusion. Infarct volume was measured in coronal brain sections stained with hematoxylin and eosin. In cerebellar granule cell cultures, MDL 74,722 resulted in a dose-dependent inhibition of TBARS formation and prevention of cell toxicity. The compound reduced infarct volume after transient occlusion of the MCA in rats by 49%. It is concluded that MDL 74,722 is a potent inhibitor of lipid peroxidation and reduces infarct volume by about one half, even when treatment is delayed. This contributes to its potential clinical usefulness.
H B van der Worp; C E Thomas; L J Kappelle; W P Hoffman; D J de Wildt; P R Bär
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Experimental neurology     Volume:  155     ISSN:  0014-4886     ISO Abbreviation:  Exp. Neurol.     Publication Date:  1999 Jan 
Date Detail:
Created Date:  1999-03-18     Completed Date:  1999-03-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370712     Medline TA:  Exp Neurol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  103-8     Citation Subset:  IM    
Copyright Information:
Copyright 1999 Academic Press.
Department of Neurology, University Hospital Utrecht, Utrecht, G 03. 228, the Netherlands.
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MeSH Terms
Brain Damage, Chronic / chemically induced*,  etiology,  metabolism,  prevention & control*
Cells, Cultured
Cerebellum / drug effects,  metabolism,  pathology
Iron* / pharmacology
Ischemic Attack, Transient / complications*
Lipid Peroxides / metabolism
Rats, Sprague-Dawley
Rats, Wistar
Vitamin E / analogs & derivatives*,  pharmacology
Reg. No./Substance:
0/Lipid Peroxides; 0/MDL 74,722; 1406-18-4/Vitamin E; 7439-89-6/Iron

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