Document Detail


OKY-046 inhibits thromboxane synthesis with no effect on brain edema and neurological status in head traumatized rats.
MedLine Citation:
PMID:  2740414     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Head trauma (HT) was induced in the left hemisphere of rats by a weight drop device. Edema was maximal 24 h after HT in the injured zone, and PGE2, TXB2 and 6-keto-PGF1 alpha were elevated in both the injured and remote areas. The effect of a specific thromboxane synthetase inhibitor, OKY-046, on the outcome of HT was studied. OKY-046, 100 mg/kg, was given to rats immediately and 8 h after HT. The neurological severity score (NSS) was evaluated at 1 h after HT, and at 24 h, just prior to sacrifice. Specific gravity (SG) of both hemispheres was measured after decapitation. Prostaglandins (PGs) were extracted from the site of injury and from the frontal lobes, remote from the injury, and assayed by RIA. Basal levels of PGE2 and 6-keto-PGF1 alpha were not reduced by the drug while basal TXB2 levels were lowered. However, the increased production due to HT of all PGs, was inhibited by OKY-046, especially that of TXB2. The ratio of TXB2/6-keto-PGF1 alpha, known to affect vascular tone, was reduced by OKY-046 treatment as a result of TXA2 synthesis inhibition. Still, no effect was found on the neurological outcome (as evaluated by the NSS), or on edema formation (expressed by reduced SG). Thus, based on the present findings increased TXA2 synthesis cannot be implicated in the pathophysiology of cerebral edema or dysfunction following HT.
Authors:
Y Shapira; G Yadid; S Cotev; E Shohami
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Prostaglandins, leukotrienes, and essential fatty acids     Volume:  36     ISSN:  0952-3278     ISO Abbreviation:  Prostaglandins Leukot. Essent. Fatty Acids     Publication Date:  1989 Apr 
Date Detail:
Created Date:  1989-08-03     Completed Date:  1989-08-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8802730     Medline TA:  Prostaglandins Leukot Essent Fatty Acids     Country:  SCOTLAND    
Other Details:
Languages:  eng     Pagination:  49-55     Citation Subset:  IM    
Affiliation:
Intensive Care Unit, Dept. of Anesthesiology, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
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MeSH Terms
Descriptor/Qualifier:
6-Ketoprostaglandin F1 alpha / metabolism
Acrylates / pharmacology*
Animals
Brain Edema / etiology,  metabolism*,  physiopathology
Brain Injuries / complications,  metabolism*,  physiopathology
Dinoprostone / metabolism
Male
Methacrylates / pharmacology*
Rats
Specific Gravity
Thromboxane B2 / biosynthesis*
Thromboxane-A Synthase / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Acrylates; 0/Methacrylates; 363-24-6/Dinoprostone; 54397-85-2/Thromboxane B2; 58962-34-8/6-Ketoprostaglandin F1 alpha; 82571-53-7/ozagrel; EC 5.3.99.5/Thromboxane-A Synthase

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


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