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    
Abstract/OtherAbstract:
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.
Authors:
H B van der Worp; C E Thomas; L J Kappelle; W P Hoffman; D J de Wildt; P R Bär
Related Documents :
15239419 - Cerebral ct and mri findings in cervicocephalic artery dissection.
11195919 - Cinema seating in right, mixed and left handers.
7707469 - Isolated vertiginous dysequilibrium due to bilateral caudal cerebellar infarction.
16580649 - Extended therapeutic time window after focal cerebral ischemia by non-competitive inhib...
7886729 - Hyperglycemia and hemorrhagic transformation of cerebral infarcts.
7491649 - Measurement of infarct size using mri predicts prognosis in middle cerebral artery infa...
11090809 - Outcome in infants with pulmonary atresia, intact ventricular septum, and right ventric...
12360159 - Effect of anemia on 1-year mortality in patients with acute myocardial infarction.
1510509 - Composite valve graft replacement of the proximal aorta: comparison of techniques in 34...
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.
Affiliation:
Department of Neurology, University Hospital Utrecht, Utrecht, G 03. 228, the Netherlands.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
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
Male
Rats
Rats, Sprague-Dawley
Rats, Wistar
Vitamin E / analogs & derivatives*,  pharmacology
Chemical
Reg. No./Substance:
0/Lipid Peroxides; 0/MDL 74,722; 1406-18-4/Vitamin E; 7439-89-6/Iron

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Sympathectomy decreases formalin-induced nociceptive responses independent of changes in peripheral ...
Next Document:  Evidence that oxidative stress is associated with the pathophysiology of inherited hydrocephalus in ...