Abstract |
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.
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Authors | H B van der Worp, C E Thomas, L J Kappelle, W P Hoffman, D J de Wildt, P R Bär |
Journal | Experimental neurology
(Exp Neurol)
Vol. 155
Issue 1
Pg. 103-8
(Jan 1999)
ISSN: 0014-4886 [Print] United States |
PMID | 9918709
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright 1999 Academic Press. |
Chemical References |
- Lipid Peroxides
- MDL 74,722
- Vitamin E
- Iron
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Topics |
- 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)
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